RARE DISEASE
Liposarcoma
Liposarcoma
Liposarcoma
Drug discovery
2
drugs
With orphan designations
Overview
Liposarcoma is a rare malignant tumor originating from adipose tissue, representing approximately 20% of adult soft tissue sarcomas [1][9]. It comprises distinct subtypes (well-differentiated, dedifferentiated, myxoid, and pleomorphic) with varying biological behaviors [1][4]. Diagnosis requires histopathological confirmation and imaging, while treatment relies on surgical resection combined with radiation and/or chemotherapy based on tumor characteristics [1][3]. Prognosis varies significantly by subtype, with 5-year survival ranging from 49% (dedifferentiated) to 94% (fibroblastic) [4][15].
Therapies
Surgery remains first-line for localized tumors, often combined with radiation (especially for myxoid subtypes) [1][3].
Chemotherapy (anthracycline-based regimens) and targeted therapies (CDK4/MDM2 inhibitors) are used for advanced/metastatic disease [3][16].
Radiation shows particular efficacy in preoperative tumor downsizing for myxoid liposarcoma [3][13].
Categories: rare neoplastic diseases
Research Papers
2,042 drug discovery papers about Liposarcoma, with 1 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,042 drug discovery papers about Liposarcoma, with 1 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-30 | Systemic Options for Recurrent Abdominal Low-grade Well-differentiated Liposarcoma.
Well-differentiated liposarcoma (WDLPS) is a low-grade malignancy characterized by an indolent clinical course and a strong tendency for local recurrence. Unlike other sarcoma subtypes, pure WDLPS has a very low metastatic potential. However, in the course of the disease, dedifferentiation may occur and is associated with a substantially higher risk of metastases and mortality. Surgery remains the cornerstone of treatment for both primary and recurrent abdominal WDLPS, when a complete resection is possible. The role of systemic therapy in WDLPS is less clearly defined. Conventional cytotoxic chemotherapy generally has limited activity in pure WDLPS, and most clinical trials have included both WDLPS with dedifferentiated liposarcoma (DDLPS) or other liposarcoma subtypes, making the data for pure WDLPS difficult to interpret. Therefore, in clinical practice, we consider systemic treatment for patients with unresectable, symptomatic disease and in cases of repeated recurrences in which further local treatment is not possible. For selected patients with indolent and asymptomatic disease, active surveillance remains an appropriate strategy. The recent development of treatments directed against molecular alterations in WDLPS, namely CDK4 and MDM2 amplifications, have opened up a new era in the systemic treatment of this disease. Among these, anti-CDK4 agent palbociclib has shown the most mature clinical evidence to date, including recent results of overall survival data. MDM2 inhibition and combinations targeting both CDK4 and MDM2 represent promising areas which are currently under investigation. Due to the rarity of WDLPS and the lack of evidence from prospective studies, enrollment in clinical trials should be prioritized whenever possible.
2026-09-18 | Anagrelide remodels the PDE3A-SLFN12 interactome to associate with translation initiation machinery in cancer cell lines.
Phosphodiesterase 3A (PDE3A) modulators such as anagrelide induce complex formation between PDE3A and Schlafen 12 (SLFN12), selectively killing cancer cells that co-express both proteins. As PDE3A forms isoform- and cell type-specific signalosome complexes across multiple subcellular compartments, the effects of its modulation are expected to depend strongly on the surrounding protein interaction network. However, despite considerable pre-clinical and early clinical interest in PDE3A modulators, the cellular context in which these compounds act has remained poorly characterized. Using proximity-dependent biotinylation in two human cancer cell lines (SA-4, liposarcoma; HeLa, cervical adenocarcinoma), we mapped the interactomes of PDE3A, SLFN12, and the anagrelide-induced PDE3A-SLFN12 complex. Anagrelide induced 259 high-confidence interactions, most notably with ribosomal proteins and translation initiation factors, while suppressing 877 interactions, most prominently those associated with the proteasome, protein folding, and the ER membrane. Interactions were selectively induced with peripheral eukaryotic translation initiation factor 3 (eIF3) subunits eIF3A and eIF3B, while interactions with core eIF3 subunits eIF3H, eIF3L, and eIF3M were suppressed. These findings were validated by native co-immunoprecipitation across three cancer cell lines, and multiplex immunofluorescence confirmed accumulation and ribosomal redistribution of both PDE3A and SLFN12 following anagrelide treatment. AlphaFold modeling of the PDE3A-SLFN12 complex with a partial 43S pre-initiation complex predicted binding near eIF3B and the eIF2αβγ-tRNA ternary complex at the mRNA entry channel. By mapping the interactomes surrounding the drug-induced complex, our study provides important mechanistic context for how PDE3A modulators act within the cell. In our proposed model, anagrelide remodels the interactome of the PDE3A-SLFN12 complex, which relocalizes and accumulates near the mRNA entry channel of the 43S pre-initiation complex.
2026-09-13 | Inflammatory Soft Tissue Tumors: A Wolf in Sheep's Clothing.
The diagnosis of soft tissue tumors is becoming increasingly complex as the number of entities and associated ancillary studies continues to increase. Mesenchymal tumors with prominent associated inflammation are challenging, given that the pathologist might not consider soft tissue entities in the differential diagnosis. This review will cover selected inflammatory soft tissue tumors commonly encountered in surgical pathology practice or associated with recurrent diagnostic pitfalls, namely,inflammatory well-differentiated liposarcoma/atypical lipomatous tumor, angiomatoid fibrous histiocytoma, myxoinflammatory fibroblastic sarcoma, inflammatory myofibroblastic tumor, and mass-forming fibroinflammatory lesions, as well as key vascular tumors with associated inflammation. To review inflammatory soft tissue tumors most commonly encountered in surgical practice or prone to significant diagnostic challenges. This article will also cover relevant ancillary studies and provide a brief differential diagnosis. Literature review through PubMed search. With advancements in musculoskeletal medicine leading to more targeted treatments, precise histologic classification is key to improving patient outcomes. This is particularly important for inflammatory soft tissue lesions, as some malignant conditions may be mistaken for reactive processes. Achieving an accurate diagnosis relies on identifying morphologic characteristics, considering the clinical presentation, and using appropriate ancillary studies.
2026-09-07 | Update on Superficial Lipomatous Tumors, Emerging Entities and Molecular Correlation.
Lipomatous tumors are among the most common mesenchymal neoplasms. They exhibit significant variability in histologic features, anatomic location, and clinical behavior. This review focuses on superficial lipomatous neoplasms. In practice, most of the superficial lipomatous tumors are benign with possible potential for local recurrence; however, atypical and fully malignant lipomatous tumors do occur in superficial locations and may be overlooked as differential diagnosis consideration. In addition to review of histologic features of classic lipomatous tumors such as lipoma, angiolipoma and atypical lipomatous tumor/well-differentiated lipoma/dedifferentiated liposarcoma, this review explores emerging and new entities such as dysplastic lipoma/anisometric cell lipoma, atypical spindle cell and pleomorphic lipomatous tumor/dedifferentiated atypical spindle cell and pleomorphic lipomatous tumor, and expanded morphologic and molecular spectrum of lipoblastoma.
2026-09-04 | Targeting the heparan sulfate proteoglycan/heparanase axis as a novel therapeutic strategy to drive adipogenesis and block tumor growth of dedifferentiated liposarcoma.
Dedifferentiated liposarcoma (DDLPS) is an aggressive mesenchymal malignancy coexisting with a low grade well-differentiated component. Pathways implicated in liposarcoma growth and dedifferentiation are promoted by heparan sulfate (HS) proteoglycans (HSPG) and their modifying enzymes including heparanase. HSPGs serve as co-receptors enhancing tyrosine kinase signaling and tumor aggressiveness. Targeting these interactions bears promise in attenuating liposarcoma growth. We employed an investigational HS mimetic, the non-anticoagulant heparin CX-01 (dociparstat), to assess its HS competition impact on deregulated adipogenic differentiation and growth of human DDLPS cell lines and patient-derived xenografts (PDXs). Remarkably, CX-01 reduced colony formation and invasive capacities of DDLPS cell lines, inducing cytoskeleton remodeling, lipid accumulation and reactivation of adipogenic program. Mechanistic studies into the anti-DDLPS activity of CX-01 unveiled Syndecan 1 (SDC1)/heparanase system and receptor tyrosine kinase-AKT signaling as targets of cell growth inhibition and induction of differentiation. CX-01 treatment of mice harboring DDLPS PDXs attenuated tumor growth, enhanced lipid content and consistently altered the transcriptome, modulating pathways associated with tumor dedifferentiation (adipogenesis and fatty acid metabolism) and tumor-microenvironment interaction (TGFβ signaling, inflammatory response). In two independent cohorts of DDLPS patients, genes downregulated in CX-01-treated PDXs (SDC1, TIMP1, FN1, COL5A1, and MMP14), were found preeminently expressed in the dedifferentiated, compared to the well-differentiated tumor component and normal fat. This suggests a role for these genes in disease progression. Collectively, this study demonstrates the remarkable potential of HS competition to simultaneously block multiple anti-adipogenic players representing metabolic vulnerabilities, and to promote a differentiated tumor phenotype markedly less aggressive.
oligonucleotides
2026-02-27 | Targeting tRNA-Arg-TCT-4-1 suppresses cancer cell growth and tumorigenesis.
tRNAs play a critical role in protein synthesis, influencing mRNA translation dynamics to shape proteomes. Emerging evidence links dysregulated tRNA activity to cancer progression, with tRNA-Arg-TCT identified as an oncogenic driver when ectopically overexpressed in non-malignant cells. The requirement of endogenous tRNA-Arg-TCT in cancer biology, however, remains untested. Moreover, considering that the tRNA-Arg-TCT family comprises six genes in humans, the importance of an individual tRNA isodecoder in cancer remains unknown. Here, we find elevated levels of tRNA-Arg-TCT-4-1 isodecoder are associated with poor patient prognosis across multiple cancer types. We demonstrate that, using different antisense RNA strategies, specific inhibition of tRNA-Arg-TCT-4-1 suppresses the growth of glioblastoma (GBM) and liposarcoma (LPS) cancer cells. Mechanistically, we find that tRNA-Arg-TCT-4-1 inhibition leads to a codon-biased remodeling of mRNA translation and the proteome, preferentially suppressing expression of growth-promoting genes and pathways encoded by mRNAs enriched in arginine AGA codons. Strikingly, intratumoral delivery of an antisense oligonucleotide (ASO) targeting tRNA-Arg-TCT-4-1 suppresses tumor growth and extends survival in mouse xenograft experiments performed using either a human LPS cell line or a patient-derived soft tissue sarcoma model. This study provides a foundation for targeting tRNA dysregulation as a novel therapeutic approach for cancer.
2025-03-24 | Targeting FANCM by antisense oligonucleotides in ALT-positive cancers.
Effective therapies for cancers relying on the alternative lengthening of telomeres (ALT) mechanisms are still needed. Here, using CRISPR-Cas9 strategies, we validate FANCM (Fanconi anemia complementation group M) as a crucial target for ALT-associated cancers and demonstrate its importance in both in vitro and in vivo models. We further explore the use of antisense oligonucleotides (ASOs), specifically gapmers, to target FANCM mRNA. We designed and screened several gapmers, identifying effective candidates that potently reduced FANCM expression, which led to an increased ALT activity and telomeric dysfunction, concomitant with a reduced viability of ALT-positive cancer cells. Notably, gapmer 14, one of the identified ASOs, significantly impaired the viability of ALT cells and reduced tumor growth in an ALT-positive liposarcoma xenograft model, highlighting its therapeutic potential. These findings suggest that FANCM-targeting ASOs could represent a promising effective strategy for treating ALT-positive cancers.
2024-07-28 | Comprehensive Analysis of a Six-Gene Signature Predicting Survival and Immune Infiltration of Liposarcoma Patients and Deciphering Its Therapeutic Significance.
As a common soft tissue sarcoma, liposarcoma (LPS) is a heterogeneous malignant tumor derived from adipose tissue. Due to the high risk of metastasis and recurrence, the prognosis of LPS remains unfavorable. To improve clinical treatment, a robust risk prediction model is essential to evaluate the prognosis of LPS patients. By comprehensive analysis of data derived from GEO datasets, differentially expressed genes (DEGs) were obtained. Univariate and Lasso Cox regressions were subsequently employed to reveal distant recurrence-free survival (DRFS)-associated DEGs and develop a prognostic gene signature, which was assessed by Kaplan-Meier survival and ROC curve. GSEA and immune infiltration analyses were conducted to illuminate molecular mechanisms and immune correlations of this model in LPS progression. Furthermore, a correlation analysis was involved to decipher the therapeutic significance of this model for LPS. A six-gene signature was developed to predict DRFS of LPS patients and showed higher precision performance in more aggressive LPS subtypes. Then, a nomogram was further established for clinical application based on this risk model. Via GSEA, the high-risk group was significantly enriched in cell cycle-related pathways. In the LPS microenvironment, neutrophils, memory B cells and resting mast cells exhibited significant differences in cell abundance between high-risk and low-risk patients. Moreover, this model was significantly correlated with therapeutic targets. A prognostic six-gene signature was developed and significantly associated with cell cycle pathways and therapeutic target genes, which could provide new insights into risk assessment of LPS progression and therapeutic strategies for LPS patients to improve their prognosis.
2024-04-22 | Effects of bone marrow mesenchymal stem cell-conditioned medium on the proliferation and migration of liposarcoma cells.
Liposarcoma constitutes a prevalent subtype of soft tissue sarcoma, represents approximately 20% of all sarcomas. However, conventional chemotherapeutic agents have shown restricted effectiveness in treating liposarcoma patients. Accumulating evidence indicates that mesenchymal stem cells (MSCs) have the characteristic of migration to tumor site, promote or suppress tumors. How human bone marrow mesenchymal stem cells (BMSCs) contribute to liposarcoma phenotype remains poorly understood. This study aims to investigate the effects of human bone marrow mesenchymal stem cell-conditioned medium (BMSC-CM) on the proliferation and migration of liposarcoma cell lines 93T449 and SW872, as well as explore potential underlying mechanisms of BMSC-CM action on these cells. We transfected BMSCs with lentiviral constructs to knock down the transcriptional co-activator Yes-associated protein 1 (YAP1), conditioned medium (CM) obtained from BMSCs and shYAP1-BMSC, respectively. Liposarcoma cell lines 93T449 and SW872 were co-cultured with BMSC-CM or shYAP1-BMSC-CM. Cell proliferation ability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was evaluated using flow cytometric assay. A wound healing assay was used to analyze cell migration. The expression levels of YAP1, Bcl-2, and matrix metalloproteinase-2 (MMP-2) were determined by western blot assay. Co-culturing liposarcoma cell lines 93T449 and SW872 with BMSC-CM promoted tumor cell proliferation, while shYAP1-BMSC-CM significantly inhibited cell viability and migration, induced apoptosis, and downregulated Bcl-2 and MMP-2 expression. These findings provide new insights into the impact of BMSC-CM on liposarcoma and suggest its possible involvement in liposarcoma cell growth.
2023-07-04 | MicroRNA-215-5p promotes proliferation, invasion, and inhibits apoptosis in liposarcoma cells by targeting MDM2.
Liposarcoma (LPS) is one of the most common soft tissue malignancies in adults, and it is characterized by dysregulation of multiple signaling pathways, including MDM2 proto-oncogene (MDM2) amplification. MicroRNA (miRNA) regulates gene expression through incomplete complementary pairing with the 3' untranslated region of mRNAs involved in tumor progression. In this study, bioinformatics analysis, RT-qPCR, dual-luciferase reporter gene, MTT, flow cytometry, cell scratches, chamber migration, colony formation, FISH, WB, and CCK8 were used. RT-qPCR showed that the expression of MDM2 was increased when miR-215-5p was overexpressed compared with the control group. The dual-luciferase reporter gene showed that the Renilla ratio firefly fluorescence intensity was decreased in the overexpression group compared with the control group. Cell phenotype experiments revealed that the overexpression group had increased cell proliferation rate, increased apoptosis rate, increased colony formation rate, increased cell healing area ratio, and increased number of cell invasions. FISH revealed increased MDM2 expression in the overexpression group. WB suggested decreased Bax expression, increased PCNA, Bcl-2, and MDM2 expression, and decreased P53 and P21 expression in the overexpression group. In this study, we suggest that miR-215-5p can target and promote MDM2 expression, promote the proliferation and invasion of LPS cells SW-872, and inhibit apoptosis.Targeting miR-215-5p may be a novel therapeutic strategy for the treatment of LPS.
cell therapies
2026-08-27 | Deep lymphaticovenular anastomosis for refractory lymphorrhea following thigh sarcoma resection: A case report.
Lymphorrhea is a common complication following wide resection of soft tissue sarcomas of the thigh. When deep lymphatic vessels are disrupted, conservative management alone may be insufficient. Lymphaticovenular anastomosis (LVA) targeting superficial lymphatic vessels has been reported as treatment for refractory lymphorrhea, while deep LVA (d-LVA) has been reported mainly for established lymphedema. Here we extend this approach to refractory postoperative lymphorrhea. We report a 53-year-old man who underwent wide resection of a left medial thigh myxoid liposarcoma with femoral artery and vein resection, followed by femoral artery reconstruction using a contralateral small saphenous vein graft and soft tissue coverage with a pedicled rectus abdominis musculocutaneous flap. He developed profuse refractory lymphorrhea and lower extremity edema. Initial LVA targeting superficial lymphatic vessels at two sites did not improve drainage, and a concurrently placed free omental graft failed and was removed. Two-compartment lymphoscintigraphy demonstrated leakage from the deep lymphatic system near the femoral canal resection margin. On postoperative day 48, additional LVA was performed at three sites, targeting deep lymphatic vessels alongside the posterior tibial vessels together with nearby superficial lymphatic vessels, and para-SSV lymphatic vessels that communicate with the deep system through the deep fascia at the popliteal fossa. Drain output decreased from approximately 200 to 19 mL/day within seven days, and lymphoscintigraphy confirmed complete resolution of leakage. No recurrence was observed within 94 days. These findings suggest that D-LVA may be effective in managing refractory lymphorrhea, and that comprehensive evaluation of the deep lymphatic system using two-compartment lymphoscintigraphy may facilitate accurate and efficient surgical planning.
2026-05-28 | A pilot study of autologous tumor-infiltrating lymphocytes (LN-145) in adult patients with undifferentiated pleomorphic sarcoma or dedifferentiated liposarcoma.
e23566 Background: Advanced undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLS) are difficult to treat soft tissue sarcomas with response rates to first line systemic therapy between 10-30%. However, both UPS and DDLPS have been shown to have measurable tumor infiltrating lymphocyte (TIL) populations. LN-144 (lifileucel), an autologous TIL product derived from unresectable or metastatic melanoma, was shown to have an overall response rate (ORR) of 36% in heavily pretreated melanoma patients with a median DOR of 19.7 months. We hypothesized that generation and infusion of LN-145, an autologous TIL product from non-melanoma solid tumors, in this case UPS and DDLPS, would be both safe and feasible. Methods: NCT05607095 is a single center multi-cohort pilot trial with Cohort 2 enrolling patients with metastatic or unresectable UPS or DDLS to undergo autologous TIL therapy with LN-145. Eligible patients had to receive at least 1 prior line of systemic therapy, a lesion at least 1.5 cm in size available for TIL harvest, and adequate organ function and performance status (ECOG 0-1). After surgical excision of suitable tumor for TIL expansion, successful LN-145 product generation was determined by characteristics that meet pre-specified criteria in the LN-145 IND. Patients then underwent nonmyeloablative lymphodepletion with cyclophosphamide (60 mg/kg x 2 doses) and fludarabine (25 mg/m 2 x 5 doses). LN-145 was then infused and expanded with intravenous interleukin 2 (600,000 IU/kg up to 6 doses). Primary endpoints of the trial were feasibility, defined as ³6 of 10 harvested pts undergoing LN-145 therapy, and safety, defined by the incidence of Grade ³3 adverse events (AE) as measured by CTCAE v5.0. Key secondary endpoints included estimated LN-145 manufacture rates and efficacy (ORR) utilizing RECIST 1.1. Exploratory endpoints include persistence of LN-145 cells and immune correlates in tissue and peripheral blood and their potential association with objective response and toxicity. Safety and efficacy measures will be summarized using point estimates and a Clopper Pearson exact confidence interval will be used. The final results of the primary feasibility and safety endpoints and secondary feasibility endpoint for the first 10 enrolled patients as well as and preliminary secondary efficacy and exploratory correlative studies through week 12 for 7 treated patients will be reported as late-breaking abstract after data lock on March 1, 2026. Clinical trial information: NCT05607095 .
2026-01-09 | Vascular Reconstruction in Extremity Soft Tissue Sarcomas: A Systematic Review and Single-Arm Meta-Analysis.
The management of extremity soft tissue sarcomas (STS) involving major vessels presents unique challenges, historically leading to amputation. Advances in vascular reconstruction have enabled limb-sparing surgery (LSS), but outcomes and perioperative risks remain uncertain. This systematic review and meta-analysis aimed to evaluate oncologic results following LSS with vascular reconstruction in extremity STS. A systematic review and single-arm meta-analysis were performed according to PRISMA guidelines, with registration in PROSPERO. PubMed, Embase, and Cochrane Library were searched from inception to June 2025 for studies reporting outcomes in patients with extremity STS undergoing LSS with vascular reconstruction. Pooled analyses estimated limb salvage, survival, and complication rates using random-effects models. Thirty-one studies comprising 520 patients were included. Approximately 58% were male, with a mean age ranging from 29.3 to 59 years. The most common tumor localizations were the thigh (59.5%), inguinal region (15.9%), and popliteal fossa (8.6%). Liposarcoma (24.0%), synovial sarcoma (19.6%), and osteosarcoma (14.8%) were the most frequent histological subtypes. The pooled limb salvage rate was 89% (95% CI, 86%-92%), while amputation occurred in 10% (95% CI, 8%-14%). One- and 5-year overall survival rates were 89% and 62%, respectively, with disease-free survival rates of 74% and 55%. Major complications included graft thrombosis (19%), wound complications (29%), and wound infection (22%). Limb-sparing surgery with vascular reconstruction is effective for extremity STS involving major vessels, enabling high limb salvage and favorable long-term survival without compromising oncologic outcomes. However, substantial perioperative morbidity persists, underscoring the need for multidisciplinary care, careful patient selection, and prospective studies to refine indications and enhance quality of life.
2025-12-31 | An evaluation of afamitresgene autoleucel for the treatment of advanced synovial sarcoma and myxoid round cell liposarcoma.
Synovial sarcoma (SyS) and myxoid round-cell liposarcoma (MRCL) are rare, aggressive soft tissue sarcomas with poor outcomes at the advanced and metastatic stage. Novel therapeutic strategies are urgently needed. Afamitresgene autoleucel (afami-cel) is the first Food and Drug Administration (FDA)-approved, affinity-enhanced T-cell receptor (TCR) therapy targeting the cancer-testis antigen MAGE-A4 in HLA-A*02-positive patients. This review summarizes clinical evidence from one early-phase study and the pivotal phase 2 SPEARHEAD-1 trial. Afami-cel achieved objective response rates of 39% in SyS and 25% in MRCL, with durable responses exceeding 11 months in SyS. The safety profile is manageable, with hematological toxicities from lymphodepletion and predominantly low-grade cytokine release syndrome; no treatment-related deaths occurred in SPEARHEAD-1. Afami-cel represents a milestone in sarcoma therapy, establishing proof of concept for engineered TCR T-cell therapies in solid tumors. However, challenges remain regarding HLA restriction, tumor microenvironment resistance, manufacturing delays and cost. Future efforts should focus on broadening applicability, optimizing combinations, and ensuring equitable access.
2025-12-11 | Gelatin-Based Soft-Tissue Sarcoma Organoids Recapitulate Patient Tumor Characteristics.
Soft-tissue sarcoma (STS) is a rare and heterogeneous group of cancers with more than 100 histological subtypes, which makes biological understanding and therapeutic development particularly challenging. Patient-derived tumor organoid models have transformed cancer research by providing patient-representative preclinical platforms, yet their application in STS has been limited because of low establishment efficiency. To address this problem, a gelatin-based culture protocol was developed to enhance critical cellular processes, including mitochondrial function and cell adhesion, which are essential for organoid self-organization. Using this optimized system, patient-derived tumor organoids were successfully established from representative STS subtypes, such as dedifferentiated liposarcoma and leiomyosarcoma. These organoids retained the histopathological architecture and molecular characteristics of the original tumors and reflected subtype-specific oncogenic pathways, mitochondrial dynamics, and lipid metabolic signatures. Our established gelatin-based organoid culture system enables efficient establishment of patient-derived organoids from representative STS subtypes, faithfully preserving their histopathological and molecular characteristics. These models recapitulate subtype-specific oncogenic pathways, mitochondrial dynamics, and lipid metabolic signatures, providing a robust and clinically relevant preclinical platform for investigating sarcoma biology and developing personalized therapeutic strategies.
antibodies
2026-06-22 | [Impact of unplanned surgery on prognosis of myxoid liposarcoma and analysis of salvage treatment strategies].
To compare the effectiveness of different treatment strategies after unplanned surgery for myxoid liposarcoma (MLS) and explore the clinical value of salvage therapy versus planned treatment following unplanned resection. The clinical data of 37 MLS patients admitted between June 2014 and June 2024 who met the selection criteria were retrospectively analyzed. Patients were divided into three groups based on initial treatment status: the unplanned treatment group (group A, 14 cases, transferred after benign tumor excision without further treatment at external hospitals, presenting with local recurrence), the salvage planned treatment group (group B, 10 cases, transferred within 1 month after benign tumor excision at external hospitals), and the planned treatment group (group C, 13 cases, transferred without prior treatment or only after biopsy). No significant difference ( P>0.05) was observed among the three groups in baseline characteristics including age, height, weight, and maximum preoperative tumor diameter. Tumor recurrence or metastasis time were recorded. Overall survival (OS) and disease-free survival (DFS) rates were calculated using the Kaplan-Meier method with intergroup comparisons. All 37 patients were followed up 19-193 months (mean, 67.4 months). Group A exhibited higher tumor recurrence (28.6%) and metastasis rates (35.7%) than group B (10.0%, 10.0%) and group C (0, 23.1%), with significant differences in recurrence rates ( P<0.05), no significant differences existed between groups B and C ( P>0.05); metastasis rates showed no intergroup significance ( P>0.05). Group A demonstrated lower 1-/3-/5-year DFS (71.4%, 42.9%, 21.4%) than group B (100%, 88.9%, 74.1%) and group C (92.3%, 83.9%, 71.9%), with significant differences ( P<0.017), no significant difference existed between groups B and C ( P>0.017); 3-/5-year OS showed no intergroup significance ( P>0.05). Patients with MLS should undergo standard extended resection and individualized adjuvant radiotherapy and chemotherapy as soon as possible after unplanned surgery to significantly reduce the local recurrence rate. In view of the high risk of extrapulmonary metastasis, a comprehensive preoperative assessment of metastasis is required.
2026-06-18 | Tumor-infiltrating CD8+Ki-67+ and CD8+LAG-3+ T cells are associated with improved patient survival in retroperitoneal dedifferentiated liposarcomas and leiomyosarcomas.
Tumor-infiltrating immune cells play a fundamental role in shaping patient prognosis across many cancers. Retroperitoneal dedifferentiated liposarcomas (DDLPS) and leiomyosarcomas (LMS) are associated with poor prognosis, therefore, a deeper understanding of the immune landscape in these tumors is warranted to identify novel prognostic biomarkers and immunotherapeutic targets. In this exploratory study, we analyzed spatial organization, frequency, and proportions of CD8+ T cell (including activated, proliferating, and exhausted phenotypes), T helper, and macrophage subsets, and B cells in primary treatment-naive retroperitoneal DDLPS (n = 22) and LMS tissues (n = 10) using classical and multiplex immunohistochemistry. CD8+LAG-3+ T cells comprised the highest proportion of all analyzed CD8+ subsets. Their elevated density was associated with improved overall survival (OS). Moreover, higher density of CD8+Ki-67+ T cells was linked to better OS and tended to independently predict OS. Interestingly, enhanced density of regulatory T cells was associated with favorable OS. Densities and proportions of T cell subsets did not significantly differ between DDLPS and LMS. A lower density of M2-like macrophages (CD68+CD163+) was linked to better progression-free survival (PFS) and tended to serve as an independent prognostic factor. Invasive margin revealed distinct prognostic patterns compared to tumor core, where high levels of CD8+Ki-67+TCF1+ were linked to better PFS and elevated proportions of CD8+GrzB+ and CD3+T-Bet+ T cells were associated with inferior PFS. These findings highlight the clinical relevance of immune infiltration in retroperitoneal DDLPS and LMS. Moreover, they support the rationale for further exploration of the immune architecture for prognostic biomarkers and development of targeted immunotherapeutic strategies to improve the clinical outcomes of the patients.
2026-06-07 | B7-H3 membranous expression correlates with histological grading in a two-center cohort of 133 pre-treatment bone and soft tissue sarcoma samples.
B7-H3 targeted therapies are an upcoming promising treatment option for a variety of solid tumors. High levels of B7-H3 expression have only been reported for a few sarcoma subtypes in previous studies, but a systematic analysis in an untreated sarcoma cohort and across many different sarcoma subtypes has not yet been conducted. One hundred thirty-three sarcoma samples of previously untreated patients from different sarcoma entities including soft tissue sarcoma (STS, n = 103) and bone sarcoma (BS, n = 30) were collected from two sarcoma centers in South-West Germany. Samples were centrally immunohistochemically stained and assessed for membranous B7-H3 expression. For further analysis of B7-H3 expression, H-Scores were calculated. Baseline characteristics such as sex, age, histology, grading, staging as well as outcome data like treatments, event-free and overall survival were collected. B7-H3 was found to be broadly expressed (97%) across all tested sarcoma subtypes, with only four samples (3%) without B7-H3 expression. 45% of all samples had low (H-Score 1-100), 33% intermediate (H-Score 101-200) and 19% high (H-Score 201-300) membranous B7-H3 expression. Highest expression was found in pleomorphic liposarcoma (median 202.5), osteosarcoma (median 175) and angiosarcoma (median 167.5), whereas expression was lowest in myxoid and well differentiated liposarcoma (medians 44.5 & 62.5) and chondrosarcoma (median 60). H-Scores were found to significantly correlate positive with histological grading irrespective of histological sarcoma subtype. Pre-treatment B7-H3 H-Scores did predict event-free but not overall survival. B7-H3 is a promising treatment target in sarcomas as it is highly expressed particular in high grade bone and soft tissue sarcomas, such as pleomorphic liposarcomas and osteosarcomas.
2026-05-21 | Tocilizumab as a novel bridging therapy for surgery in dedifferentiated liposarcoma complicated by paraneoplastic leukemoid reaction, severe anemia, and thrombocytopenia: a case report.
Dedifferentiated liposarcoma (DDLPS) is a malignant mesenchymal tumor. While paraneoplastic leukemoid reaction (PLR) has been sporadically reported in DDLPS, its coexistence with severe anemia and thrombocytopenia, constituting a severe cytokine release syndrome (CRS), is exceedingly rare and presents a significant diagnostic and therapeutic challenge. A 56-year-old male with recurrent retroperitoneal well-differentiated liposarcoma presented with high fever, profound leukocytosis (WBC up to 43×109/L), severe anemia (Hb 30 g/L), and thrombocytopenia (platelets 10×109/L), which precluded immediate surgery. Extensive workup ruled out infection and hematological malignancies. The clinical picture was consistent with a tumor-induced CRS, evidenced by markedly elevated interleukin-6 (IL-6) and C-reactive protein (CRP). Following a multidisciplinary discussion, the patient received intravenous tocilizumab (an IL-6 receptor antagonist) and methylprednisolone. His fever resolved rapidly, and hematological parameters improved significantly, facilitating successful tumor resection. Postoperative pathology confirmed DDLPS. All paraneoplastic symptoms and laboratory abnormalities normalized after surgery. However, at the second follow-up, tumor recurrence was observed along with a marked elevation of the WBC, which again decreased following the subsequent surgical resection. This case highlights that DDLPS can trigger CRS, which manifests with clinical features mimicking severe infection and leading to critical cytopenias that complicate surgical management. IL-6 pathway blockade with agents such as tocilizumab may be an effective bridging therapy to stabilize the systemic inflammatory state and create a safe window for surgical intervention.
2026-05-19 | Durable remission of metastatic myxoid liposarcoma following the cautious addition of pembrolizumab to ongoing pazopanib treatment: A case report.
Responses to conventional treatments, like chemotherapy and targeted agents, are generally infrequent, and of brief duration in patients with metastatic soft tissue sarcomas. We present a case of metastatic myxoid liposarcoma that achieved biopsy-proven complete remission with minimal toxicity following the addition of pembrolizumab to pazopanib as fourth-line treatment. This regimen resulted in significant tumor regression following just five doses. After 15 doses of pembrolizumab, radiographs demonstrated an ongoing response, with stable residual lesions, and a biopsy of a sacral lesion confirmed a pathologic complete remission. The patient subsequently discontinued all therapies and remains in an ongoing unmaintained remission. The combination of pembrolizumab and pazopanib demonstrated unexpected clinical benefit with minimal toxicity, suggesting that it may be worthy of further investigation in myxoid liposarcoma and possibly other histologic subtypes of STS.
other
2026-07-28 | Identifying subsets of patients with retroperitoneal sarcoma who benefit from radiotherapy: an Interpretable AI reanalysis of the STRASS randomised trial.
The European Organisation for Research and Treatment of Cancer's STRASS trial, the only completed randomised study of preoperative radiotherapy in retroperitoneal sarcoma, showed no overall benefit. Its subgroup analysis has been interpreted as supporting radiotherapy for all patients with liposarcoma, whereas the STREXIT extension has been interpreted as supporting radiotherapy for well differentiated liposarcoma and low-grade or intermediate-grade dedifferentiated liposarcoma. We aimed to identify subsets of patients who might benefit from preoperative radiotherapy and to quantify this benefit in terms of abdominal recurrence. In this artificial intelligence (AI)-based reanalysis of the STRASS dataset, we trained a random survival forest model on all 266 randomly assigned patients (radiotherapy plus surgery vs surgery alone) to predict 5-year abdominal recurrence-free survival under both treatment options, based on pretreatment variables. These predictions were used to fit an optimal policy tree (OPT) that partitions patients into nodes by predicted abdominal recurrence-free survival benefit from radiotherapy. We then compared outcomes in OPT-defined subgroups, STRASS subgroups, and STREXIT subgroups through Kaplan-Meier curves, and Fine-Gray competing-risks models within STRASS. The OPT partitioned the cohort into seven subgroups; three subgroups (152 of 266 patients) were predicted to benefit from radiotherapy, and for two of these subgroups the benefit was statistically significant: patients with well differentiated liposarcoma aged 60 years or younger and patients with dedifferentiated liposarcoma who underwent curative-intent surgery. In these two subgroups combined, 3-year abdominal recurrence-free survival was 79% (95% CI 70-89) with radiotherapy versus 58% (48-72) without (hazard ratio [HR] 0·40 [95% CI 0·22-0·71], p=0·0016), and the cumulative incidence of abdominal recurrence was significantly lower with radiotherapy (17% [95% CI 9-27] vs 33% [22-45] without radiotherapy; HR 0·40, p=0·0090). Inverse probability of censoring weight-adjusted 5-year abdominal recurrence-free survival estimates showed similar absolute gains (25·6 percentage points). A Cox model found a significant radiotherapy-age interaction (p=0·012). By contrast, STRASS-defined and STREXIT-defined radiotherapy subgroups did not show significant abdominal recurrence-free survival improvement when re-evaluated within STRASS. The AI-guided partition of STRASS identified younger patients with well differentiated liposarcoma and patients with dedifferentiated liposarcoma and curative-intent surgery as subgroups in which radiotherapy appears to meaningfully improve abdominal recurrence-free survival, whereas radiotherapy strategies for all well differentiated liposarcoma and low-grade or intermediate-grade dedifferentiated liposarcoma were not supported by the randomised controlled trial data. These findings argue for a more selective use of preoperative radiotherapy in retroperitoneal sarcoma and provide a concrete basis for focused future trials, which, if successful, could substantiate these findings before these strategies become standards of care. National Cancer Institute and Memorial Sloan Kettering Cancer Center.
2026-04-03 | Spatially-resolved single cell atlas of liposarcoma reveals lineage hierarchies, immune niches, and regulatory circuits.
Well-differentiated and dedifferentiated liposarcoma (WDLPS and DDLPS) exhibit markedly different clinical behaviors, with DDLPS showing greater aggressiveness, higher recurrence and metastasis rates, and worse outcomes. Using single-nucleus multiome sequencing, epigenomic profiling, and spatial transcriptomics, we characterized cellular and epigenetic heterogeneity between these subtypes at single-cell and spatial resolution. We found distinct phenotypic states reflecting altered lineage differentiation and plasticity: DDLPS is dominated by early-differentiated progenitor-like cells, sclerotic WDLPS displays broader mesenchymal lineage plasticity, and adipocytic WDLPS contains abundant committed adipocytes. The DDLPS immune microenvironment was dominated by immunosuppressive macrophages, whereas WDLPS harbored more T cells and inflammatory macrophages. Notably, sclerotic WDLPS displayed intermediate cellular and molecular features, suggesting it may represent a distinct WDLPS subtype. Importantly, we identified novel gene regulatory circuits underlying each state, including FABP4/PPARG programs in adipocytic WDLPS, GLI2/TCF7L2/RBPJ/KLF7 programs in sclerotic WDLPS, and KLF7/FOSL2/SP3/GLI2/RBPJ programs in DDLPS. H3K27ac-marked enhancers were enriched near adipocytic marker genes in WDLPS and mesenchymal markers in DDLPS. Together, these findings reveal the cellular heterogeneity of tumor and immune compartments across liposarcoma subtypes and identify regulatory programs driving their differentiation states.
2026-01-28 | Molecular and Immune Mechanisms Governing Cancer Metastasis, Including Dormancy, Microenvironmental Niches, and Tumor-Specific Programs.
Metastasis is still the leading cause of cancer-related death. It happens when disseminated tumor cells (DTCs) successfully navigate a series of steps and adapt to the unique conditions of distant organs. In this review, key molecular and immune mechanisms that shape metastatic spread, long-term survival, and eventual outgrowth are examined, with a focus on how tumor-intrinsic programs interact with extracellular matrix (ECM) remodeling, angiogenesis, and immune regulation. Gene networks that sustain tumor-cell plasticity and invasion are described, including EMT-linked transcription factors such as SNAIL and TWIST, as well as broader transcriptional regulators like SP1. Also, how epigenetic mechanisms, such as EZH2 activity, DNA methylation, chromatin remodeling, and noncoding RNAs, lock in pro-metastatic states and support adaptation under therapeutic pressure. Finally, proteases and matrix-modifying enzymes that physically and biochemically reshape tissues, including MMPs, uPA, cathepsins, LOX/LOXL2, and heparinase, are discussed for their roles in releasing stored growth signals and building permissive niches that enable seeding and colonization. In parallel, immune-evasion strategies that protect circulating and newly seeded tumor cells are discussed, including platelet-mediated shielding, suppressive myeloid populations, checkpoint signaling, and stromal barriers that exclude effector lymphocytes. A major focus is metastatic dormancy, cellular, angiogenic, and immune-mediated, framed as a reversible survival state regulated by stress signaling, adhesion cues, metabolic rewiring, and niche constraints, and as a key determinant of late relapse. Tumor-specific metastatic programs across mesenchymal malignancies (osteosarcoma, chondrosarcoma, and liposarcoma) and selected high-burden cancers (melanoma, hepatocellular carcinoma, glioblastoma, and breast cancer) are highlighted, emphasizing shared principles and divergent organotropisms. Emerging therapeutic strategies that target both the "seed" and the "soil" are also discussed, including immunotherapy combinations, stromal/ECM normalization, chemokine-axis inhibition, epigenetic reprogramming, and liquid-biopsy-enabled minimal residual disease monitoring, to prevent reactivation and improve durable control of metastatic disease.
2026-01-23 | Subtype-specific characteristics and outcomes of liposarcoma: A population-based study using Japan's National Cancer Registry.
Liposarcoma demonstrates significant biological and clinical heterogeneity across subtypes, yet optimal treatment strategies remain controversial. We evaluated subtype-specific treatment outcomes and hospital volume effects using population-based registry data. We conducted a population-based cohort study analyzing 6,678 patients with liposarcoma diagnosed between 2016 and 2019 from the Japanese National Cancer Registry. Subtype-specific clinical characteristics, treatment patterns, and survival outcomes were evaluated using Cox regression and Kaplan-Meier methods. Propensity score matching was performed to assess radiotherapy and chemotherapy effectiveness while controlling for confounding variables. Well-differentiated liposarcoma was most common (46.2 %), followed by dedifferentiated (27.8 %), myxoid (10.8 %), and pleomorphic (3.2 %) subtypes. Myxoid liposarcomas predominantly affected patients aged <60 years (63.8 %). Multivariate analysis identified male sex (HR 1.264, p = 0.008), older age (HR 3.307, p < 0.001), retroperitoneal location (HR 1.861, p < 0.001), distant disease (HR 6.091, p < 0.001), and treatment at low-volume hospitals (HR 1.381, p = 0.001) as independent poor prognostic factors. Propensity score-matched analysis demonstrated improved survival with radiotherapy in dedifferentiated liposarcomas (3-year survival: 76.5 % vs. 66.1 %, p = 0.022) and with chemotherapy in pleomorphic liposarcomas (3-year survival: 87.5 % vs. 68.8 %, p = 0.038). Treatment efficacy varies significantly across liposarcoma subtypes, with potential survival benefits of radiotherapy in dedifferentiated subtypes and chemotherapy in pleomorphic subtypes. These findings support subtype-guided treatment approaches and suggest benefits of centralized care for optimal therapy implementation.
2026-01-21 | Myxoid liposarcoma of right popliteal fossa: Case report and review.
Myxoid liposarcoma (MLS) accounts for 30% of liposarcomas and typically arises in the thigh, but rarely arises in the popliteal fossa. Managing giant, neurovascular-abutting MLS in young adults is poorly characterized. A 35-year-old man presented with a right popliteal mass growing over > 6 years, accompanied by progressive swelling and incomplete flexion of the right knee. He denied smoking, denied alcohol use, and had no family history of malignancy. magnetic resonance imaging showed a 179 × 154 × 99 mm multilocular cystic-solid lesion abutting/partly encasing the popliteal vessels and contacting the sciatic/common peroneal nerves. Preoperative cytology suggested benignity; definitive resection revealed MLS grade II with 20% round cell component (R1 margin adjacent to the vessel plane). En bloc resection with function-preserving R1 margins was performed given neurovascular involvement; popliteal artery/vein and nerves were preserved. Postoperative external-beam radiotherapy was delivered to 60 Gy in 30 fractions (2 Gy/fraction). At the 18-month follow-up, progressive recovery of knee joint range of motion was observed, and no local recurrence or metastasis at 18 months. Magnetic resonance imaging at 6 and 18 months showed no local-recurrence or metastasis. This case demonstrates that in young patients with popliteal MLS closely related to neurovascular structures, function-preserving R1 resection plus postoperative 60 Gy can achieve local-control while maintaining limb function, provided meticulous technique and guideline-concordant surveillance.
small molecules
2026-09-30 | Systemic Options for Recurrent Abdominal Low-grade Well-differentiated Liposarcoma.
Well-differentiated liposarcoma (WDLPS) is a low-grade malignancy characterized by an indolent clinical course and a strong tendency for local recurrence. Unlike other sarcoma subtypes, pure WDLPS has a very low metastatic potential. However, in the course of the disease, dedifferentiation may occur and is associated with a substantially higher risk of metastases and mortality. Surgery remains the cornerstone of treatment for both primary and recurrent abdominal WDLPS, when a complete resection is possible. The role of systemic therapy in WDLPS is less clearly defined. Conventional cytotoxic chemotherapy generally has limited activity in pure WDLPS, and most clinical trials have included both WDLPS with dedifferentiated liposarcoma (DDLPS) or other liposarcoma subtypes, making the data for pure WDLPS difficult to interpret. Therefore, in clinical practice, we consider systemic treatment for patients with unresectable, symptomatic disease and in cases of repeated recurrences in which further local treatment is not possible. For selected patients with indolent and asymptomatic disease, active surveillance remains an appropriate strategy. The recent development of treatments directed against molecular alterations in WDLPS, namely CDK4 and MDM2 amplifications, have opened up a new era in the systemic treatment of this disease. Among these, anti-CDK4 agent palbociclib has shown the most mature clinical evidence to date, including recent results of overall survival data. MDM2 inhibition and combinations targeting both CDK4 and MDM2 represent promising areas which are currently under investigation. Due to the rarity of WDLPS and the lack of evidence from prospective studies, enrollment in clinical trials should be prioritized whenever possible.
2026-09-18 | Anagrelide remodels the PDE3A-SLFN12 interactome to associate with translation initiation machinery in cancer cell lines.
Phosphodiesterase 3A (PDE3A) modulators such as anagrelide induce complex formation between PDE3A and Schlafen 12 (SLFN12), selectively killing cancer cells that co-express both proteins. As PDE3A forms isoform- and cell type-specific signalosome complexes across multiple subcellular compartments, the effects of its modulation are expected to depend strongly on the surrounding protein interaction network. However, despite considerable pre-clinical and early clinical interest in PDE3A modulators, the cellular context in which these compounds act has remained poorly characterized. Using proximity-dependent biotinylation in two human cancer cell lines (SA-4, liposarcoma; HeLa, cervical adenocarcinoma), we mapped the interactomes of PDE3A, SLFN12, and the anagrelide-induced PDE3A-SLFN12 complex. Anagrelide induced 259 high-confidence interactions, most notably with ribosomal proteins and translation initiation factors, while suppressing 877 interactions, most prominently those associated with the proteasome, protein folding, and the ER membrane. Interactions were selectively induced with peripheral eukaryotic translation initiation factor 3 (eIF3) subunits eIF3A and eIF3B, while interactions with core eIF3 subunits eIF3H, eIF3L, and eIF3M were suppressed. These findings were validated by native co-immunoprecipitation across three cancer cell lines, and multiplex immunofluorescence confirmed accumulation and ribosomal redistribution of both PDE3A and SLFN12 following anagrelide treatment. AlphaFold modeling of the PDE3A-SLFN12 complex with a partial 43S pre-initiation complex predicted binding near eIF3B and the eIF2αβγ-tRNA ternary complex at the mRNA entry channel. By mapping the interactomes surrounding the drug-induced complex, our study provides important mechanistic context for how PDE3A modulators act within the cell. In our proposed model, anagrelide remodels the interactome of the PDE3A-SLFN12 complex, which relocalizes and accumulates near the mRNA entry channel of the 43S pre-initiation complex.
2026-09-13 | Inflammatory Soft Tissue Tumors: A Wolf in Sheep's Clothing.
The diagnosis of soft tissue tumors is becoming increasingly complex as the number of entities and associated ancillary studies continues to increase. Mesenchymal tumors with prominent associated inflammation are challenging, given that the pathologist might not consider soft tissue entities in the differential diagnosis. This review will cover selected inflammatory soft tissue tumors commonly encountered in surgical pathology practice or associated with recurrent diagnostic pitfalls, namely,inflammatory well-differentiated liposarcoma/atypical lipomatous tumor, angiomatoid fibrous histiocytoma, myxoinflammatory fibroblastic sarcoma, inflammatory myofibroblastic tumor, and mass-forming fibroinflammatory lesions, as well as key vascular tumors with associated inflammation. To review inflammatory soft tissue tumors most commonly encountered in surgical practice or prone to significant diagnostic challenges. This article will also cover relevant ancillary studies and provide a brief differential diagnosis. Literature review through PubMed search. With advancements in musculoskeletal medicine leading to more targeted treatments, precise histologic classification is key to improving patient outcomes. This is particularly important for inflammatory soft tissue lesions, as some malignant conditions may be mistaken for reactive processes. Achieving an accurate diagnosis relies on identifying morphologic characteristics, considering the clinical presentation, and using appropriate ancillary studies.
2026-09-07 | Update on Superficial Lipomatous Tumors, Emerging Entities and Molecular Correlation.
Lipomatous tumors are among the most common mesenchymal neoplasms. They exhibit significant variability in histologic features, anatomic location, and clinical behavior. This review focuses on superficial lipomatous neoplasms. In practice, most of the superficial lipomatous tumors are benign with possible potential for local recurrence; however, atypical and fully malignant lipomatous tumors do occur in superficial locations and may be overlooked as differential diagnosis consideration. In addition to review of histologic features of classic lipomatous tumors such as lipoma, angiolipoma and atypical lipomatous tumor/well-differentiated lipoma/dedifferentiated liposarcoma, this review explores emerging and new entities such as dysplastic lipoma/anisometric cell lipoma, atypical spindle cell and pleomorphic lipomatous tumor/dedifferentiated atypical spindle cell and pleomorphic lipomatous tumor, and expanded morphologic and molecular spectrum of lipoblastoma.
2026-09-04 | Targeting the heparan sulfate proteoglycan/heparanase axis as a novel therapeutic strategy to drive adipogenesis and block tumor growth of dedifferentiated liposarcoma.
Dedifferentiated liposarcoma (DDLPS) is an aggressive mesenchymal malignancy coexisting with a low grade well-differentiated component. Pathways implicated in liposarcoma growth and dedifferentiation are promoted by heparan sulfate (HS) proteoglycans (HSPG) and their modifying enzymes including heparanase. HSPGs serve as co-receptors enhancing tyrosine kinase signaling and tumor aggressiveness. Targeting these interactions bears promise in attenuating liposarcoma growth. We employed an investigational HS mimetic, the non-anticoagulant heparin CX-01 (dociparstat), to assess its HS competition impact on deregulated adipogenic differentiation and growth of human DDLPS cell lines and patient-derived xenografts (PDXs). Remarkably, CX-01 reduced colony formation and invasive capacities of DDLPS cell lines, inducing cytoskeleton remodeling, lipid accumulation and reactivation of adipogenic program. Mechanistic studies into the anti-DDLPS activity of CX-01 unveiled Syndecan 1 (SDC1)/heparanase system and receptor tyrosine kinase-AKT signaling as targets of cell growth inhibition and induction of differentiation. CX-01 treatment of mice harboring DDLPS PDXs attenuated tumor growth, enhanced lipid content and consistently altered the transcriptome, modulating pathways associated with tumor dedifferentiation (adipogenesis and fatty acid metabolism) and tumor-microenvironment interaction (TGFβ signaling, inflammatory response). In two independent cohorts of DDLPS patients, genes downregulated in CX-01-treated PDXs (SDC1, TIMP1, FN1, COL5A1, and MMP14), were found preeminently expressed in the dedifferentiated, compared to the well-differentiated tumor component and normal fat. This suggests a role for these genes in disease progression. Collectively, this study demonstrates the remarkable potential of HS competition to simultaneously block multiple anti-adipogenic players representing metabolic vulnerabilities, and to promote a differentiated tumor phenotype markedly less aggressive.
oligonucleotides
2026-02-27 | Targeting tRNA-Arg-TCT-4-1 suppresses cancer cell growth and tumorigenesis.
tRNAs play a critical role in protein synthesis, influencing mRNA translation dynamics to shape proteomes. Emerging evidence links dysregulated tRNA activity to cancer progression, with tRNA-Arg-TCT identified as an oncogenic driver when ectopically overexpressed in non-malignant cells. The requirement of endogenous tRNA-Arg-TCT in cancer biology, however, remains untested. Moreover, considering that the tRNA-Arg-TCT family comprises six genes in humans, the importance of an individual tRNA isodecoder in cancer remains unknown. Here, we find elevated levels of tRNA-Arg-TCT-4-1 isodecoder are associated with poor patient prognosis across multiple cancer types. We demonstrate that, using different antisense RNA strategies, specific inhibition of tRNA-Arg-TCT-4-1 suppresses the growth of glioblastoma (GBM) and liposarcoma (LPS) cancer cells. Mechanistically, we find that tRNA-Arg-TCT-4-1 inhibition leads to a codon-biased remodeling of mRNA translation and the proteome, preferentially suppressing expression of growth-promoting genes and pathways encoded by mRNAs enriched in arginine AGA codons. Strikingly, intratumoral delivery of an antisense oligonucleotide (ASO) targeting tRNA-Arg-TCT-4-1 suppresses tumor growth and extends survival in mouse xenograft experiments performed using either a human LPS cell line or a patient-derived soft tissue sarcoma model. This study provides a foundation for targeting tRNA dysregulation as a novel therapeutic approach for cancer.
2025-03-24 | Targeting FANCM by antisense oligonucleotides in ALT-positive cancers.
Effective therapies for cancers relying on the alternative lengthening of telomeres (ALT) mechanisms are still needed. Here, using CRISPR-Cas9 strategies, we validate FANCM (Fanconi anemia complementation group M) as a crucial target for ALT-associated cancers and demonstrate its importance in both in vitro and in vivo models. We further explore the use of antisense oligonucleotides (ASOs), specifically gapmers, to target FANCM mRNA. We designed and screened several gapmers, identifying effective candidates that potently reduced FANCM expression, which led to an increased ALT activity and telomeric dysfunction, concomitant with a reduced viability of ALT-positive cancer cells. Notably, gapmer 14, one of the identified ASOs, significantly impaired the viability of ALT cells and reduced tumor growth in an ALT-positive liposarcoma xenograft model, highlighting its therapeutic potential. These findings suggest that FANCM-targeting ASOs could represent a promising effective strategy for treating ALT-positive cancers.
2024-07-28 | Comprehensive Analysis of a Six-Gene Signature Predicting Survival and Immune Infiltration of Liposarcoma Patients and Deciphering Its Therapeutic Significance.
As a common soft tissue sarcoma, liposarcoma (LPS) is a heterogeneous malignant tumor derived from adipose tissue. Due to the high risk of metastasis and recurrence, the prognosis of LPS remains unfavorable. To improve clinical treatment, a robust risk prediction model is essential to evaluate the prognosis of LPS patients. By comprehensive analysis of data derived from GEO datasets, differentially expressed genes (DEGs) were obtained. Univariate and Lasso Cox regressions were subsequently employed to reveal distant recurrence-free survival (DRFS)-associated DEGs and develop a prognostic gene signature, which was assessed by Kaplan-Meier survival and ROC curve. GSEA and immune infiltration analyses were conducted to illuminate molecular mechanisms and immune correlations of this model in LPS progression. Furthermore, a correlation analysis was involved to decipher the therapeutic significance of this model for LPS. A six-gene signature was developed to predict DRFS of LPS patients and showed higher precision performance in more aggressive LPS subtypes. Then, a nomogram was further established for clinical application based on this risk model. Via GSEA, the high-risk group was significantly enriched in cell cycle-related pathways. In the LPS microenvironment, neutrophils, memory B cells and resting mast cells exhibited significant differences in cell abundance between high-risk and low-risk patients. Moreover, this model was significantly correlated with therapeutic targets. A prognostic six-gene signature was developed and significantly associated with cell cycle pathways and therapeutic target genes, which could provide new insights into risk assessment of LPS progression and therapeutic strategies for LPS patients to improve their prognosis.
2024-04-22 | Effects of bone marrow mesenchymal stem cell-conditioned medium on the proliferation and migration of liposarcoma cells.
Liposarcoma constitutes a prevalent subtype of soft tissue sarcoma, represents approximately 20% of all sarcomas. However, conventional chemotherapeutic agents have shown restricted effectiveness in treating liposarcoma patients. Accumulating evidence indicates that mesenchymal stem cells (MSCs) have the characteristic of migration to tumor site, promote or suppress tumors. How human bone marrow mesenchymal stem cells (BMSCs) contribute to liposarcoma phenotype remains poorly understood. This study aims to investigate the effects of human bone marrow mesenchymal stem cell-conditioned medium (BMSC-CM) on the proliferation and migration of liposarcoma cell lines 93T449 and SW872, as well as explore potential underlying mechanisms of BMSC-CM action on these cells. We transfected BMSCs with lentiviral constructs to knock down the transcriptional co-activator Yes-associated protein 1 (YAP1), conditioned medium (CM) obtained from BMSCs and shYAP1-BMSC, respectively. Liposarcoma cell lines 93T449 and SW872 were co-cultured with BMSC-CM or shYAP1-BMSC-CM. Cell proliferation ability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was evaluated using flow cytometric assay. A wound healing assay was used to analyze cell migration. The expression levels of YAP1, Bcl-2, and matrix metalloproteinase-2 (MMP-2) were determined by western blot assay. Co-culturing liposarcoma cell lines 93T449 and SW872 with BMSC-CM promoted tumor cell proliferation, while shYAP1-BMSC-CM significantly inhibited cell viability and migration, induced apoptosis, and downregulated Bcl-2 and MMP-2 expression. These findings provide new insights into the impact of BMSC-CM on liposarcoma and suggest its possible involvement in liposarcoma cell growth.
2023-07-04 | MicroRNA-215-5p promotes proliferation, invasion, and inhibits apoptosis in liposarcoma cells by targeting MDM2.
Liposarcoma (LPS) is one of the most common soft tissue malignancies in adults, and it is characterized by dysregulation of multiple signaling pathways, including MDM2 proto-oncogene (MDM2) amplification. MicroRNA (miRNA) regulates gene expression through incomplete complementary pairing with the 3' untranslated region of mRNAs involved in tumor progression. In this study, bioinformatics analysis, RT-qPCR, dual-luciferase reporter gene, MTT, flow cytometry, cell scratches, chamber migration, colony formation, FISH, WB, and CCK8 were used. RT-qPCR showed that the expression of MDM2 was increased when miR-215-5p was overexpressed compared with the control group. The dual-luciferase reporter gene showed that the Renilla ratio firefly fluorescence intensity was decreased in the overexpression group compared with the control group. Cell phenotype experiments revealed that the overexpression group had increased cell proliferation rate, increased apoptosis rate, increased colony formation rate, increased cell healing area ratio, and increased number of cell invasions. FISH revealed increased MDM2 expression in the overexpression group. WB suggested decreased Bax expression, increased PCNA, Bcl-2, and MDM2 expression, and decreased P53 and P21 expression in the overexpression group. In this study, we suggest that miR-215-5p can target and promote MDM2 expression, promote the proliferation and invasion of LPS cells SW-872, and inhibit apoptosis.Targeting miR-215-5p may be a novel therapeutic strategy for the treatment of LPS.
cell therapies
2026-08-27 | Deep lymphaticovenular anastomosis for refractory lymphorrhea following thigh sarcoma resection: A case report.
Lymphorrhea is a common complication following wide resection of soft tissue sarcomas of the thigh. When deep lymphatic vessels are disrupted, conservative management alone may be insufficient. Lymphaticovenular anastomosis (LVA) targeting superficial lymphatic vessels has been reported as treatment for refractory lymphorrhea, while deep LVA (d-LVA) has been reported mainly for established lymphedema. Here we extend this approach to refractory postoperative lymphorrhea. We report a 53-year-old man who underwent wide resection of a left medial thigh myxoid liposarcoma with femoral artery and vein resection, followed by femoral artery reconstruction using a contralateral small saphenous vein graft and soft tissue coverage with a pedicled rectus abdominis musculocutaneous flap. He developed profuse refractory lymphorrhea and lower extremity edema. Initial LVA targeting superficial lymphatic vessels at two sites did not improve drainage, and a concurrently placed free omental graft failed and was removed. Two-compartment lymphoscintigraphy demonstrated leakage from the deep lymphatic system near the femoral canal resection margin. On postoperative day 48, additional LVA was performed at three sites, targeting deep lymphatic vessels alongside the posterior tibial vessels together with nearby superficial lymphatic vessels, and para-SSV lymphatic vessels that communicate with the deep system through the deep fascia at the popliteal fossa. Drain output decreased from approximately 200 to 19 mL/day within seven days, and lymphoscintigraphy confirmed complete resolution of leakage. No recurrence was observed within 94 days. These findings suggest that D-LVA may be effective in managing refractory lymphorrhea, and that comprehensive evaluation of the deep lymphatic system using two-compartment lymphoscintigraphy may facilitate accurate and efficient surgical planning.
2026-05-28 | A pilot study of autologous tumor-infiltrating lymphocytes (LN-145) in adult patients with undifferentiated pleomorphic sarcoma or dedifferentiated liposarcoma.
e23566 Background: Advanced undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLS) are difficult to treat soft tissue sarcomas with response rates to first line systemic therapy between 10-30%. However, both UPS and DDLPS have been shown to have measurable tumor infiltrating lymphocyte (TIL) populations. LN-144 (lifileucel), an autologous TIL product derived from unresectable or metastatic melanoma, was shown to have an overall response rate (ORR) of 36% in heavily pretreated melanoma patients with a median DOR of 19.7 months. We hypothesized that generation and infusion of LN-145, an autologous TIL product from non-melanoma solid tumors, in this case UPS and DDLPS, would be both safe and feasible. Methods: NCT05607095 is a single center multi-cohort pilot trial with Cohort 2 enrolling patients with metastatic or unresectable UPS or DDLS to undergo autologous TIL therapy with LN-145. Eligible patients had to receive at least 1 prior line of systemic therapy, a lesion at least 1.5 cm in size available for TIL harvest, and adequate organ function and performance status (ECOG 0-1). After surgical excision of suitable tumor for TIL expansion, successful LN-145 product generation was determined by characteristics that meet pre-specified criteria in the LN-145 IND. Patients then underwent nonmyeloablative lymphodepletion with cyclophosphamide (60 mg/kg x 2 doses) and fludarabine (25 mg/m 2 x 5 doses). LN-145 was then infused and expanded with intravenous interleukin 2 (600,000 IU/kg up to 6 doses). Primary endpoints of the trial were feasibility, defined as ³6 of 10 harvested pts undergoing LN-145 therapy, and safety, defined by the incidence of Grade ³3 adverse events (AE) as measured by CTCAE v5.0. Key secondary endpoints included estimated LN-145 manufacture rates and efficacy (ORR) utilizing RECIST 1.1. Exploratory endpoints include persistence of LN-145 cells and immune correlates in tissue and peripheral blood and their potential association with objective response and toxicity. Safety and efficacy measures will be summarized using point estimates and a Clopper Pearson exact confidence interval will be used. The final results of the primary feasibility and safety endpoints and secondary feasibility endpoint for the first 10 enrolled patients as well as and preliminary secondary efficacy and exploratory correlative studies through week 12 for 7 treated patients will be reported as late-breaking abstract after data lock on March 1, 2026. Clinical trial information: NCT05607095 .
2026-01-09 | Vascular Reconstruction in Extremity Soft Tissue Sarcomas: A Systematic Review and Single-Arm Meta-Analysis.
The management of extremity soft tissue sarcomas (STS) involving major vessels presents unique challenges, historically leading to amputation. Advances in vascular reconstruction have enabled limb-sparing surgery (LSS), but outcomes and perioperative risks remain uncertain. This systematic review and meta-analysis aimed to evaluate oncologic results following LSS with vascular reconstruction in extremity STS. A systematic review and single-arm meta-analysis were performed according to PRISMA guidelines, with registration in PROSPERO. PubMed, Embase, and Cochrane Library were searched from inception to June 2025 for studies reporting outcomes in patients with extremity STS undergoing LSS with vascular reconstruction. Pooled analyses estimated limb salvage, survival, and complication rates using random-effects models. Thirty-one studies comprising 520 patients were included. Approximately 58% were male, with a mean age ranging from 29.3 to 59 years. The most common tumor localizations were the thigh (59.5%), inguinal region (15.9%), and popliteal fossa (8.6%). Liposarcoma (24.0%), synovial sarcoma (19.6%), and osteosarcoma (14.8%) were the most frequent histological subtypes. The pooled limb salvage rate was 89% (95% CI, 86%-92%), while amputation occurred in 10% (95% CI, 8%-14%). One- and 5-year overall survival rates were 89% and 62%, respectively, with disease-free survival rates of 74% and 55%. Major complications included graft thrombosis (19%), wound complications (29%), and wound infection (22%). Limb-sparing surgery with vascular reconstruction is effective for extremity STS involving major vessels, enabling high limb salvage and favorable long-term survival without compromising oncologic outcomes. However, substantial perioperative morbidity persists, underscoring the need for multidisciplinary care, careful patient selection, and prospective studies to refine indications and enhance quality of life.
2025-12-31 | An evaluation of afamitresgene autoleucel for the treatment of advanced synovial sarcoma and myxoid round cell liposarcoma.
Synovial sarcoma (SyS) and myxoid round-cell liposarcoma (MRCL) are rare, aggressive soft tissue sarcomas with poor outcomes at the advanced and metastatic stage. Novel therapeutic strategies are urgently needed. Afamitresgene autoleucel (afami-cel) is the first Food and Drug Administration (FDA)-approved, affinity-enhanced T-cell receptor (TCR) therapy targeting the cancer-testis antigen MAGE-A4 in HLA-A*02-positive patients. This review summarizes clinical evidence from one early-phase study and the pivotal phase 2 SPEARHEAD-1 trial. Afami-cel achieved objective response rates of 39% in SyS and 25% in MRCL, with durable responses exceeding 11 months in SyS. The safety profile is manageable, with hematological toxicities from lymphodepletion and predominantly low-grade cytokine release syndrome; no treatment-related deaths occurred in SPEARHEAD-1. Afami-cel represents a milestone in sarcoma therapy, establishing proof of concept for engineered TCR T-cell therapies in solid tumors. However, challenges remain regarding HLA restriction, tumor microenvironment resistance, manufacturing delays and cost. Future efforts should focus on broadening applicability, optimizing combinations, and ensuring equitable access.
2025-12-11 | Gelatin-Based Soft-Tissue Sarcoma Organoids Recapitulate Patient Tumor Characteristics.
Soft-tissue sarcoma (STS) is a rare and heterogeneous group of cancers with more than 100 histological subtypes, which makes biological understanding and therapeutic development particularly challenging. Patient-derived tumor organoid models have transformed cancer research by providing patient-representative preclinical platforms, yet their application in STS has been limited because of low establishment efficiency. To address this problem, a gelatin-based culture protocol was developed to enhance critical cellular processes, including mitochondrial function and cell adhesion, which are essential for organoid self-organization. Using this optimized system, patient-derived tumor organoids were successfully established from representative STS subtypes, such as dedifferentiated liposarcoma and leiomyosarcoma. These organoids retained the histopathological architecture and molecular characteristics of the original tumors and reflected subtype-specific oncogenic pathways, mitochondrial dynamics, and lipid metabolic signatures. Our established gelatin-based organoid culture system enables efficient establishment of patient-derived organoids from representative STS subtypes, faithfully preserving their histopathological and molecular characteristics. These models recapitulate subtype-specific oncogenic pathways, mitochondrial dynamics, and lipid metabolic signatures, providing a robust and clinically relevant preclinical platform for investigating sarcoma biology and developing personalized therapeutic strategies.
antibodies
2026-06-22 | [Impact of unplanned surgery on prognosis of myxoid liposarcoma and analysis of salvage treatment strategies].
To compare the effectiveness of different treatment strategies after unplanned surgery for myxoid liposarcoma (MLS) and explore the clinical value of salvage therapy versus planned treatment following unplanned resection. The clinical data of 37 MLS patients admitted between June 2014 and June 2024 who met the selection criteria were retrospectively analyzed. Patients were divided into three groups based on initial treatment status: the unplanned treatment group (group A, 14 cases, transferred after benign tumor excision without further treatment at external hospitals, presenting with local recurrence), the salvage planned treatment group (group B, 10 cases, transferred within 1 month after benign tumor excision at external hospitals), and the planned treatment group (group C, 13 cases, transferred without prior treatment or only after biopsy). No significant difference ( P>0.05) was observed among the three groups in baseline characteristics including age, height, weight, and maximum preoperative tumor diameter. Tumor recurrence or metastasis time were recorded. Overall survival (OS) and disease-free survival (DFS) rates were calculated using the Kaplan-Meier method with intergroup comparisons. All 37 patients were followed up 19-193 months (mean, 67.4 months). Group A exhibited higher tumor recurrence (28.6%) and metastasis rates (35.7%) than group B (10.0%, 10.0%) and group C (0, 23.1%), with significant differences in recurrence rates ( P<0.05), no significant differences existed between groups B and C ( P>0.05); metastasis rates showed no intergroup significance ( P>0.05). Group A demonstrated lower 1-/3-/5-year DFS (71.4%, 42.9%, 21.4%) than group B (100%, 88.9%, 74.1%) and group C (92.3%, 83.9%, 71.9%), with significant differences ( P<0.017), no significant difference existed between groups B and C ( P>0.017); 3-/5-year OS showed no intergroup significance ( P>0.05). Patients with MLS should undergo standard extended resection and individualized adjuvant radiotherapy and chemotherapy as soon as possible after unplanned surgery to significantly reduce the local recurrence rate. In view of the high risk of extrapulmonary metastasis, a comprehensive preoperative assessment of metastasis is required.
2026-06-18 | Tumor-infiltrating CD8+Ki-67+ and CD8+LAG-3+ T cells are associated with improved patient survival in retroperitoneal dedifferentiated liposarcomas and leiomyosarcomas.
Tumor-infiltrating immune cells play a fundamental role in shaping patient prognosis across many cancers. Retroperitoneal dedifferentiated liposarcomas (DDLPS) and leiomyosarcomas (LMS) are associated with poor prognosis, therefore, a deeper understanding of the immune landscape in these tumors is warranted to identify novel prognostic biomarkers and immunotherapeutic targets. In this exploratory study, we analyzed spatial organization, frequency, and proportions of CD8+ T cell (including activated, proliferating, and exhausted phenotypes), T helper, and macrophage subsets, and B cells in primary treatment-naive retroperitoneal DDLPS (n = 22) and LMS tissues (n = 10) using classical and multiplex immunohistochemistry. CD8+LAG-3+ T cells comprised the highest proportion of all analyzed CD8+ subsets. Their elevated density was associated with improved overall survival (OS). Moreover, higher density of CD8+Ki-67+ T cells was linked to better OS and tended to independently predict OS. Interestingly, enhanced density of regulatory T cells was associated with favorable OS. Densities and proportions of T cell subsets did not significantly differ between DDLPS and LMS. A lower density of M2-like macrophages (CD68+CD163+) was linked to better progression-free survival (PFS) and tended to serve as an independent prognostic factor. Invasive margin revealed distinct prognostic patterns compared to tumor core, where high levels of CD8+Ki-67+TCF1+ were linked to better PFS and elevated proportions of CD8+GrzB+ and CD3+T-Bet+ T cells were associated with inferior PFS. These findings highlight the clinical relevance of immune infiltration in retroperitoneal DDLPS and LMS. Moreover, they support the rationale for further exploration of the immune architecture for prognostic biomarkers and development of targeted immunotherapeutic strategies to improve the clinical outcomes of the patients.
2026-06-07 | B7-H3 membranous expression correlates with histological grading in a two-center cohort of 133 pre-treatment bone and soft tissue sarcoma samples.
B7-H3 targeted therapies are an upcoming promising treatment option for a variety of solid tumors. High levels of B7-H3 expression have only been reported for a few sarcoma subtypes in previous studies, but a systematic analysis in an untreated sarcoma cohort and across many different sarcoma subtypes has not yet been conducted. One hundred thirty-three sarcoma samples of previously untreated patients from different sarcoma entities including soft tissue sarcoma (STS, n = 103) and bone sarcoma (BS, n = 30) were collected from two sarcoma centers in South-West Germany. Samples were centrally immunohistochemically stained and assessed for membranous B7-H3 expression. For further analysis of B7-H3 expression, H-Scores were calculated. Baseline characteristics such as sex, age, histology, grading, staging as well as outcome data like treatments, event-free and overall survival were collected. B7-H3 was found to be broadly expressed (97%) across all tested sarcoma subtypes, with only four samples (3%) without B7-H3 expression. 45% of all samples had low (H-Score 1-100), 33% intermediate (H-Score 101-200) and 19% high (H-Score 201-300) membranous B7-H3 expression. Highest expression was found in pleomorphic liposarcoma (median 202.5), osteosarcoma (median 175) and angiosarcoma (median 167.5), whereas expression was lowest in myxoid and well differentiated liposarcoma (medians 44.5 & 62.5) and chondrosarcoma (median 60). H-Scores were found to significantly correlate positive with histological grading irrespective of histological sarcoma subtype. Pre-treatment B7-H3 H-Scores did predict event-free but not overall survival. B7-H3 is a promising treatment target in sarcomas as it is highly expressed particular in high grade bone and soft tissue sarcomas, such as pleomorphic liposarcomas and osteosarcomas.
2026-05-21 | Tocilizumab as a novel bridging therapy for surgery in dedifferentiated liposarcoma complicated by paraneoplastic leukemoid reaction, severe anemia, and thrombocytopenia: a case report.
Dedifferentiated liposarcoma (DDLPS) is a malignant mesenchymal tumor. While paraneoplastic leukemoid reaction (PLR) has been sporadically reported in DDLPS, its coexistence with severe anemia and thrombocytopenia, constituting a severe cytokine release syndrome (CRS), is exceedingly rare and presents a significant diagnostic and therapeutic challenge. A 56-year-old male with recurrent retroperitoneal well-differentiated liposarcoma presented with high fever, profound leukocytosis (WBC up to 43×109/L), severe anemia (Hb 30 g/L), and thrombocytopenia (platelets 10×109/L), which precluded immediate surgery. Extensive workup ruled out infection and hematological malignancies. The clinical picture was consistent with a tumor-induced CRS, evidenced by markedly elevated interleukin-6 (IL-6) and C-reactive protein (CRP). Following a multidisciplinary discussion, the patient received intravenous tocilizumab (an IL-6 receptor antagonist) and methylprednisolone. His fever resolved rapidly, and hematological parameters improved significantly, facilitating successful tumor resection. Postoperative pathology confirmed DDLPS. All paraneoplastic symptoms and laboratory abnormalities normalized after surgery. However, at the second follow-up, tumor recurrence was observed along with a marked elevation of the WBC, which again decreased following the subsequent surgical resection. This case highlights that DDLPS can trigger CRS, which manifests with clinical features mimicking severe infection and leading to critical cytopenias that complicate surgical management. IL-6 pathway blockade with agents such as tocilizumab may be an effective bridging therapy to stabilize the systemic inflammatory state and create a safe window for surgical intervention.
2026-05-19 | Durable remission of metastatic myxoid liposarcoma following the cautious addition of pembrolizumab to ongoing pazopanib treatment: A case report.
Responses to conventional treatments, like chemotherapy and targeted agents, are generally infrequent, and of brief duration in patients with metastatic soft tissue sarcomas. We present a case of metastatic myxoid liposarcoma that achieved biopsy-proven complete remission with minimal toxicity following the addition of pembrolizumab to pazopanib as fourth-line treatment. This regimen resulted in significant tumor regression following just five doses. After 15 doses of pembrolizumab, radiographs demonstrated an ongoing response, with stable residual lesions, and a biopsy of a sacral lesion confirmed a pathologic complete remission. The patient subsequently discontinued all therapies and remains in an ongoing unmaintained remission. The combination of pembrolizumab and pazopanib demonstrated unexpected clinical benefit with minimal toxicity, suggesting that it may be worthy of further investigation in myxoid liposarcoma and possibly other histologic subtypes of STS.
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2026-07-28 | Identifying subsets of patients with retroperitoneal sarcoma who benefit from radiotherapy: an Interpretable AI reanalysis of the STRASS randomised trial.
The European Organisation for Research and Treatment of Cancer's STRASS trial, the only completed randomised study of preoperative radiotherapy in retroperitoneal sarcoma, showed no overall benefit. Its subgroup analysis has been interpreted as supporting radiotherapy for all patients with liposarcoma, whereas the STREXIT extension has been interpreted as supporting radiotherapy for well differentiated liposarcoma and low-grade or intermediate-grade dedifferentiated liposarcoma. We aimed to identify subsets of patients who might benefit from preoperative radiotherapy and to quantify this benefit in terms of abdominal recurrence. In this artificial intelligence (AI)-based reanalysis of the STRASS dataset, we trained a random survival forest model on all 266 randomly assigned patients (radiotherapy plus surgery vs surgery alone) to predict 5-year abdominal recurrence-free survival under both treatment options, based on pretreatment variables. These predictions were used to fit an optimal policy tree (OPT) that partitions patients into nodes by predicted abdominal recurrence-free survival benefit from radiotherapy. We then compared outcomes in OPT-defined subgroups, STRASS subgroups, and STREXIT subgroups through Kaplan-Meier curves, and Fine-Gray competing-risks models within STRASS. The OPT partitioned the cohort into seven subgroups; three subgroups (152 of 266 patients) were predicted to benefit from radiotherapy, and for two of these subgroups the benefit was statistically significant: patients with well differentiated liposarcoma aged 60 years or younger and patients with dedifferentiated liposarcoma who underwent curative-intent surgery. In these two subgroups combined, 3-year abdominal recurrence-free survival was 79% (95% CI 70-89) with radiotherapy versus 58% (48-72) without (hazard ratio [HR] 0·40 [95% CI 0·22-0·71], p=0·0016), and the cumulative incidence of abdominal recurrence was significantly lower with radiotherapy (17% [95% CI 9-27] vs 33% [22-45] without radiotherapy; HR 0·40, p=0·0090). Inverse probability of censoring weight-adjusted 5-year abdominal recurrence-free survival estimates showed similar absolute gains (25·6 percentage points). A Cox model found a significant radiotherapy-age interaction (p=0·012). By contrast, STRASS-defined and STREXIT-defined radiotherapy subgroups did not show significant abdominal recurrence-free survival improvement when re-evaluated within STRASS. The AI-guided partition of STRASS identified younger patients with well differentiated liposarcoma and patients with dedifferentiated liposarcoma and curative-intent surgery as subgroups in which radiotherapy appears to meaningfully improve abdominal recurrence-free survival, whereas radiotherapy strategies for all well differentiated liposarcoma and low-grade or intermediate-grade dedifferentiated liposarcoma were not supported by the randomised controlled trial data. These findings argue for a more selective use of preoperative radiotherapy in retroperitoneal sarcoma and provide a concrete basis for focused future trials, which, if successful, could substantiate these findings before these strategies become standards of care. National Cancer Institute and Memorial Sloan Kettering Cancer Center.
2026-04-03 | Spatially-resolved single cell atlas of liposarcoma reveals lineage hierarchies, immune niches, and regulatory circuits.
Well-differentiated and dedifferentiated liposarcoma (WDLPS and DDLPS) exhibit markedly different clinical behaviors, with DDLPS showing greater aggressiveness, higher recurrence and metastasis rates, and worse outcomes. Using single-nucleus multiome sequencing, epigenomic profiling, and spatial transcriptomics, we characterized cellular and epigenetic heterogeneity between these subtypes at single-cell and spatial resolution. We found distinct phenotypic states reflecting altered lineage differentiation and plasticity: DDLPS is dominated by early-differentiated progenitor-like cells, sclerotic WDLPS displays broader mesenchymal lineage plasticity, and adipocytic WDLPS contains abundant committed adipocytes. The DDLPS immune microenvironment was dominated by immunosuppressive macrophages, whereas WDLPS harbored more T cells and inflammatory macrophages. Notably, sclerotic WDLPS displayed intermediate cellular and molecular features, suggesting it may represent a distinct WDLPS subtype. Importantly, we identified novel gene regulatory circuits underlying each state, including FABP4/PPARG programs in adipocytic WDLPS, GLI2/TCF7L2/RBPJ/KLF7 programs in sclerotic WDLPS, and KLF7/FOSL2/SP3/GLI2/RBPJ programs in DDLPS. H3K27ac-marked enhancers were enriched near adipocytic marker genes in WDLPS and mesenchymal markers in DDLPS. Together, these findings reveal the cellular heterogeneity of tumor and immune compartments across liposarcoma subtypes and identify regulatory programs driving their differentiation states.
2026-01-28 | Molecular and Immune Mechanisms Governing Cancer Metastasis, Including Dormancy, Microenvironmental Niches, and Tumor-Specific Programs.
Metastasis is still the leading cause of cancer-related death. It happens when disseminated tumor cells (DTCs) successfully navigate a series of steps and adapt to the unique conditions of distant organs. In this review, key molecular and immune mechanisms that shape metastatic spread, long-term survival, and eventual outgrowth are examined, with a focus on how tumor-intrinsic programs interact with extracellular matrix (ECM) remodeling, angiogenesis, and immune regulation. Gene networks that sustain tumor-cell plasticity and invasion are described, including EMT-linked transcription factors such as SNAIL and TWIST, as well as broader transcriptional regulators like SP1. Also, how epigenetic mechanisms, such as EZH2 activity, DNA methylation, chromatin remodeling, and noncoding RNAs, lock in pro-metastatic states and support adaptation under therapeutic pressure. Finally, proteases and matrix-modifying enzymes that physically and biochemically reshape tissues, including MMPs, uPA, cathepsins, LOX/LOXL2, and heparinase, are discussed for their roles in releasing stored growth signals and building permissive niches that enable seeding and colonization. In parallel, immune-evasion strategies that protect circulating and newly seeded tumor cells are discussed, including platelet-mediated shielding, suppressive myeloid populations, checkpoint signaling, and stromal barriers that exclude effector lymphocytes. A major focus is metastatic dormancy, cellular, angiogenic, and immune-mediated, framed as a reversible survival state regulated by stress signaling, adhesion cues, metabolic rewiring, and niche constraints, and as a key determinant of late relapse. Tumor-specific metastatic programs across mesenchymal malignancies (osteosarcoma, chondrosarcoma, and liposarcoma) and selected high-burden cancers (melanoma, hepatocellular carcinoma, glioblastoma, and breast cancer) are highlighted, emphasizing shared principles and divergent organotropisms. Emerging therapeutic strategies that target both the "seed" and the "soil" are also discussed, including immunotherapy combinations, stromal/ECM normalization, chemokine-axis inhibition, epigenetic reprogramming, and liquid-biopsy-enabled minimal residual disease monitoring, to prevent reactivation and improve durable control of metastatic disease.
2026-01-23 | Subtype-specific characteristics and outcomes of liposarcoma: A population-based study using Japan's National Cancer Registry.
Liposarcoma demonstrates significant biological and clinical heterogeneity across subtypes, yet optimal treatment strategies remain controversial. We evaluated subtype-specific treatment outcomes and hospital volume effects using population-based registry data. We conducted a population-based cohort study analyzing 6,678 patients with liposarcoma diagnosed between 2016 and 2019 from the Japanese National Cancer Registry. Subtype-specific clinical characteristics, treatment patterns, and survival outcomes were evaluated using Cox regression and Kaplan-Meier methods. Propensity score matching was performed to assess radiotherapy and chemotherapy effectiveness while controlling for confounding variables. Well-differentiated liposarcoma was most common (46.2 %), followed by dedifferentiated (27.8 %), myxoid (10.8 %), and pleomorphic (3.2 %) subtypes. Myxoid liposarcomas predominantly affected patients aged <60 years (63.8 %). Multivariate analysis identified male sex (HR 1.264, p = 0.008), older age (HR 3.307, p < 0.001), retroperitoneal location (HR 1.861, p < 0.001), distant disease (HR 6.091, p < 0.001), and treatment at low-volume hospitals (HR 1.381, p = 0.001) as independent poor prognostic factors. Propensity score-matched analysis demonstrated improved survival with radiotherapy in dedifferentiated liposarcomas (3-year survival: 76.5 % vs. 66.1 %, p = 0.022) and with chemotherapy in pleomorphic liposarcomas (3-year survival: 87.5 % vs. 68.8 %, p = 0.038). Treatment efficacy varies significantly across liposarcoma subtypes, with potential survival benefits of radiotherapy in dedifferentiated subtypes and chemotherapy in pleomorphic subtypes. These findings support subtype-guided treatment approaches and suggest benefits of centralized care for optimal therapy implementation.
2026-01-21 | Myxoid liposarcoma of right popliteal fossa: Case report and review.
Myxoid liposarcoma (MLS) accounts for 30% of liposarcomas and typically arises in the thigh, but rarely arises in the popliteal fossa. Managing giant, neurovascular-abutting MLS in young adults is poorly characterized. A 35-year-old man presented with a right popliteal mass growing over > 6 years, accompanied by progressive swelling and incomplete flexion of the right knee. He denied smoking, denied alcohol use, and had no family history of malignancy. magnetic resonance imaging showed a 179 × 154 × 99 mm multilocular cystic-solid lesion abutting/partly encasing the popliteal vessels and contacting the sciatic/common peroneal nerves. Preoperative cytology suggested benignity; definitive resection revealed MLS grade II with 20% round cell component (R1 margin adjacent to the vessel plane). En bloc resection with function-preserving R1 margins was performed given neurovascular involvement; popliteal artery/vein and nerves were preserved. Postoperative external-beam radiotherapy was delivered to 60 Gy in 30 fractions (2 Gy/fraction). At the 18-month follow-up, progressive recovery of knee joint range of motion was observed, and no local recurrence or metastasis at 18 months. Magnetic resonance imaging at 6 and 18 months showed no local-recurrence or metastasis. This case demonstrates that in young patients with popliteal MLS closely related to neurovascular structures, function-preserving R1 resection plus postoperative 60 Gy can achieve local-control while maintaining limb function, provided meticulous technique and guideline-concordant surveillance.
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Drug Discovery Landscape
2 orphan drug designations for Liposarcoma.
2 orphan drug designations for Liposarcoma.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
N-(4-(1-cyclopropyl-4-fluoro-2-methyl-1H-benzo[d]imidazol-6-yl)-5-fluoropyrimidin-2-yl)-6-(2-(dimethylamino)ethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-2-amine maleate | small molecules | FDA | Shanghai Pharma Biotherapeutics USA Inc. | |
milademetan | small molecules | FDA | Rain Oncology Inc. |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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