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
2,029 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:
2,029 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
2026-08-06 | Dedifferentiated Liposarcoma Presenting as Primary Diffuse Peritoneal Sarcomatosis: A Case Report and Literature Review.
Dedifferentiated liposarcoma (DDLPS) typically presents as a solitary retroperitoneal mass; diffuse granular and nodular peritoneal sarcomatosis as the inaugural manifestation is exceptional. We report such a case to highlight a critical diagnostic consideration: distinguishing primary sarcomatous peritoneal dissemination from the more common epithelial peritoneal carcinomatosis. A 72-year-old Chinese man with no prior abdominal surgery presented with incidentally discovered multifocal intra-abdominal masses. CT demonstrated multiple peritoneal and retroperitoneal masses with encasement of the jejunum and transmural infiltration of the descending colon, and a retroperitoneal plaque abutting the left kidney. CT-guided biopsy confirmed DDLPS via MDM2 and CDK4 amplification on fluorescence in situ hybridization. Multidisciplinary team consensus directed surgical exploration for impending dual-site bowel obstruction. Laparotomy revealed diffuse granular and nodular peritoneal deposits (Peritoneal Cancer Index 28/39); cytoreductive surgery achieved a completeness of cytoreduction score of 2. Histopathology confirmed FNCLCC Grade III DDLPS. Postoperative next-generation sequencing demonstrated high-level co-amplification of CDK4, MDM2, TSPAN31, CCND2, MDM4, and RAC1, with microsatellite stability and tumor mutational burden of 0 mutations/Mb. DDLPS can present with primary diffuse peritoneal sarcomatosis even with a retroperitoneal component. When diffuse peritoneal implants yield an epithelial-marker-negative spindle cell neoplasm on biopsy, sarcoma must be considered in the differential diagnosis and FISH for MDM2/CDK4 should be performed to avoid misdiagnosis as peritoneal carcinomatosis from gastric, colorectal, or ovarian cancer.
2026-07-23 | Transcriptional Heterogeneity in Dedifferentiated Liposarcoma Reveals Distinct Cell-Cycle Subtypes.
Dedifferentiated liposarcoma (DDLPS) is characterized by amplification of cyclin-dependent kinase 4 (CDK4). However, responses to CDK4/6 inhibition have been heterogeneous. We sought to determine whether transcriptional heterogeneity in cell-cycle regulators define biologically distinct subtypes of DDLPS that contribute to CDK4/6 inhibitor sensitivity. RNA sequencing data from The Cancer Genome Atlas sarcoma cohort (TCGA-SARC) were analyzed to identify DDLPS tumors (N = 57). Expression of key cell-cycle regulators was evaluated according to CDK4 expression to assess differences in cell-cycle regulation. Unsupervised clustering of cell-cycle regulators was performed to identify transcriptional subgroups and pathway activity across clusters was assessed. Initial comparison of tumors with high versus low CDK4 expression demonstrated differential expression of cell-cycle regulators, including increased CDK2 and CDKN2A expression in CDK4-high tumors. Unsupervised clustering identified three transcriptionally distinct subgroups characterized by patterns of CDK4 and CDK2 expression. These clusters were associated with divergent pathway activity profiles. One subgroup demonstrated high CDK4 expression with relatively low CDK2 activation and enrichment of inflammatory signaling pathways, suggesting continued reliance on the CDK4-RB axis. A second subgroup demonstrated concurrent activation of CDK4 and CDK2 alongside a proliferative transcriptional program, consistent with potential CDK2-mediated bypass of CDK4 signaling. A third subgroup demonstrated relatively low expression of both CDK4 and CDK2 with enrichment of hormone-associated signaling pathways. DDLPS tumors exhibit distinct transcriptional states within the CDK4-RB regulatory network that may influence tumor dependence on CDK4 signaling. This may impact sensitivity to CDK4/6 inhibition and explain heterogeneous outcomes.
2026-07-21 | MDM4 Amplification in Liposarcoma: A Rare Finding or an Underrecognized Pathway?
Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) is typically characterized by MDM2 and/or CDK4 amplification. However, a subset lacks these alterations, suggesting alternative oncogenic drivers. We report a patient with recurrent retroperitoneal WDLPS who developed multiple relapses over more than 25 years. Histology demonstrated a well-differentiated morphology with extensive myxoid change, without evidence of dedifferentiation. Molecular profiling using next-generation sequencing (NGS) identified MDM4 amplification, together with mutations in PIK3CA and TERT. This finding supports MDM4 as a potential alternative driver in liposarcomagenesis, possibly correlating with a more indolent clinical course. Recognition of this rare alteration is important for accurate diagnosis and may have future therapeutic implications.
2026-07-13 | Early local recurrence of well-differentiated liposarcoma of the hypopharynx in a young adult: a case report and literature review.
Well-differentiated liposarcoma (WDLPS), also termed atypical lipomatous tumor, is a low-grade malignant adipocytic neoplasm characterized by indolent growth, limited metastatic potential, and a propensity for local recurrence. Primary WDLPS arising in the hypopharyngeal region is exceptionally rare, particularly in young adults, and may clinically mimic benign submucosal lesions. We report the case of a 24-year-old man who presented with a one-month history of persistent foreign body sensation in the throat. Flexible laryngoscopy revealed a smooth submucosal mass arising from the left hypopharyngeal region, and contrast-enhanced magnetic resonance imaging demonstrated a well-circumscribed enhancing lesion without cervical lymphadenopathy. The mass was excised transorally under general anesthesia. Histopathological examination showed mature adipocytic proliferation with atypical stromal cells, and immunohistochemistry demonstrated positivity for MDM2, CDK4, CD34, and p16. Fluorescence in situ hybridization confirmed MDM2 gene amplification, establishing the diagnosis of WDLPS. Although the early postoperative course was uneventful and initial follow-up showed satisfactory mucosal healing, serial laryngoscopic examinations at 2, 2.5, and 4 months after surgery revealed early local recurrence at the surgical site. This case highlights that hypopharyngeal WDLPS can occur in young adults and may recur early even after apparently complete transoral excision. Accurate diagnosis requires integration of histopathology, MDM2/CDK4 immunohistochemistry, and molecular confirmation of MDM2 amplification. Close endoscopic and radiological surveillance is essential for early detection of local recurrence.
2026-07-13 | A Case Report: Retroperitoneal dedifferentiated liposarcoma with heterologous myogenic differentiation and testicular metastasis.
Dedifferentiated liposarcoma (DDLPS) is the most common retroperitoneal soft tissue sarcoma, characterized by MDM2 and CDK4 gene co-amplification. However, DDLPS with heterologous myogenic differentiation is extremely rare and poses a significant diagnostic challenge due to its expression of myogenic markers such as desmin, myogenin, and MyoD1, which can easily lead to misclassification as primary rhabdomyosarcoma. Testicular metastasis of DDLPS is even rarer, with only isolated case reports documented in the literature. We report a case of a 46-year-old male who presented with a large retroperitoneal mass without testicular involvement on initial imaging. He underwent en bloc resection of the retroperitoneal tumor including right nephrectomy and right hemicolectomy. Ten days postoperatively, he developed a right scrotal mass, prompting radical orchiectomy. Initial pathological evaluation suggested rhabdomyosarcoma based on desmin and MyoD1 positivity. However, subsequent expert pathological consultation with fluorescence in situ hybridization (FISH) analysis revealed MDM2 and CDK4 gene amplification in both specimens, establishing the final diagnosis of DDLPS with prominent heterologous myogenic differentiation. Postoperative chest CT demonstrated early pulmonary metastases, underscoring the aggressive nature of this tumor. This case highlights the critical importance of MDM2/CDK4 FISH testing in accurately diagnosing DDLPS with heterologous differentiation, particularly when myogenic markers are expressed, to avoid misdiagnosis and guide appropriate management.
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
2026-05-28 | 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.
2025-10-22 | Neo-inguinal reconstruction: algorithm for layered vascularized tissue coverage using plug flap following oncologic inguinal resection.
Tumors in the inguinal region are challenging to resect and reconstruct, especially when the inguinal ligament is violated. Without the shelving effect of the inguinal ligament in the setting of extensive local tissue deficit and major vessel exposure, there is an elevated risk of postoperative bowel incarceration and potential damage to the femoral neurovascular bundle. This is a retrospective case series of patients who underwent radical resection of pelvic tumors with inguinal ligament involvement. In addition to mesh placement, local flaps were layered to function as soft tissue plugs to avoid bowel herniation. Six patients with a mean age of 65.5 years were included. There were five cases of liposarcoma and one case of metastatic lung cancer. The inguinal ligament was resected in 4 patients and divided in 2 patients. The rectus abdominus was used in 3 cases and the rectus femoris in 2 cases to cover the mesh. The omentum was used in 2 patients and the sartorius in 1 patient to act as a soft tissue plug. The first inguinal ligament resection patient did not have a soft tissue plug, which resulted in incarcerated inguinal hernia. One patient with soft tissue plug developed inguinal hernia 19 months after surgery after returning to heavy labor work but did not require surgery. Patients undergoing extensive oncologic resection can benefit from neo-inguinal reconstruction by implementing a soft tissue plug between the femoral vessels and the mesh.
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
2026-04-03 | 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.
2025-10-02 | Identification of Guanine-Quadruplex-Binding Peptides from the RGG3 Domain of TLS/FUS.
Guanine quadruplexes (G4s) are non-canonical nucleic acid structures that have emerged as attractive therapeutic targets owing to their involvement in diverse biological processes. Additionally, peptides derived from G4-binding proteins provide promising platforms for selective G4 recognition. In this study, we explored the G4-binding capacity of arginine-glycine-glycine (RGG)-rich sequences derived from the RGG3 domain translocated in liposarcoma/fused in sarcoma (TLS/FUS), a known G4 RNA binding protein. In this study, we synthesized a library of overlapping 15-mer peptides and evaluated their G4-binding affinities. Among the 10 evaluated native sequences, several peptides demonstrated measurable affinities toward G4 RNA structures, with STK5-1 exhibiting the highest G4-binding affinity. Furthermore, to investigate the impact of conformational constraints on G4 recognition, we introduced (E)-methylalkene dipeptide isosteres (MADIs) into selected Gly-Gly motifs, generating a series of RGG peptidomimetics. Subsequent binding assays revealed that some of these MADI peptidomimetics exhibited enhanced affinity and selectivity compared with their unmodified counterparts. Our findings offer new insights into the sequence and structural features governing G4-binding, establishing a foundation for the further development of peptide-based G4 ligands.
2025-07-04 | Recurrent giant retroperitoneal dedifferentiated liposarcoma requiring challenging multiorgan resection: a case report.
Dedifferentiated liposarcoma is a rare, aggressive subtype of liposarcoma known for its high recurrence rate and local invasiveness. This case demonstrates the challenges in managing a rapidly recurring dedifferentiated liposarcoma and underscores the need for improved surveillance and additional treatment options. A 57-year-old non-Hispanic white male presented in November 2023 with a 2-month history of intermittent fevers, nonproductive cough, and lower abdominal discomfort. Imaging revealed a 12 cm × 12 cm × 16 cm retroperitoneal mass, confirmed to be a high-grade dedifferentiated liposarcoma. Initial surgical resection in December 2023 removed the tumor, which was densely adhered to the left kidney. Despite adjuvant chemotherapy, follow-up imaging in July 2024 showed tumor recurrence with a 15 cm × 14 cm × 21 cm multiloculated cystic mass extending from the spleen to the lower pole of the kidney, as well as a 12 cm × 6 cm × 15 cm mass inferior to the left kidney. Owing to the extensive local invasion, a second surgery in August 2024 required a left nephrectomy, splenectomy, hemicolectomy, and distal pancreatectomy. The tumor's proximity to the abdominal aorta and invasion into the psoas muscle posed significant surgical challenges, requiring careful resection. This case highlights the aggressive nature of high-grade dedifferentiated liposarcoma and its resistance to chemotherapy. Surgical resection remains the primary treatment option, but the recurrence emphasizes the need for more effective therapies. The case further illustrates the complexity of multiorgan involvement in recurrent dedifferentiated liposarcoma and the critical role of experienced oncologic surgeons in managing these cases. More research is necessary to develop alternative treatments that can better control tumor progression and improve patient outcomes.
2025-03-28 | Expression of Cancer-Testis Antigens MAGE-A1, MAGE-A4, NY-ESO-1 and PRAME in Bone and Soft Tissue Sarcomas: The Experience From a Single Center in China.
Sarcomas are a heterogeneous group of malignancies, low disease-control levels and the limited durability of responses have prompted the exploration of various novel immunotherapeutic approaches. To preliminarily explore the feasibility of cancer vaccines based on cancer testis antigen in the immunotherapy of sarcomas, we investigate the expression of Cancer/Testis Antigens (CTA) MAGE-A4, PRAME, MAGE-A1, KK-LC-1, and NY-ESO-1 in bone and soft tissue sarcomas, with the aim of assessing their potential for use in sarcoma immunotherapy and determining their expression levels in different subtypes. We employed immunohistochemistry and multiplex immunostaining microarrays (MI chips) to assess the expression of MAGE-A4, PRAME, MAGE-A1, KK-LC-1, and NY-ESO-1 in 21 cases of undifferentiated pleomorphic sarcoma (UPS), 26 cases of smooth muscle sarcoma, 28 cases of liposarcoma, 40 cases of osteosarcoma (OS), and 13 cases of chondrosarcoma. MAGE-A1 showed the highest expression in osteosarcoma (32.50%), while it was lower in liposarcoma and undifferentiated pleomorphic sarcoma (10.71% and 10.00%) and undetectable in chondrosarcoma. MAGE-A4 expression was elevated in osteosarcoma and undifferentiated pleomorphic sarcoma (40.00% and 33.00%), but lower in liposarcoma and smooth muscle sarcoma (17.00% and 33.00%). NY-ESO-1 expression was relatively low across all sarcoma subtypes. PRAME expression was highest in undifferentiated pleomorphic sarcoma (47.62%) and low in chondrosarcoma (7.69%). None of the sarcomas expressed KK-LC-1. Additionally, while there was no statistically significant correlation between CTA expression and patient age or gender, some differences related to age and gender were observed. CTA expression in bone and soft tissue sarcomas was correlated with both CTA type and sarcoma subtype, showing relatively high levels of expression in undifferentiated pleomorphic sarcoma (UPS) and osteosarcoma (OS). The poly-expression of MAGE-A4, PRAME, and MAGE-A1 across all subtypes suggests that these antigens may serve as potential targets for sarcoma-specific immunotherapy.
2025-03-27 | Anti-CD137 agonist antibody-independent and clinically feasible preparation of tumor-infiltrating lymphocytes from soft tissue sarcoma and osteosarcoma.
Tumor infiltrating lymphocytes (TILs) therapy has been proved for treatment of metastatic melanoma and is under investigation for other types of solid tumors. However, these successes are threatened by discontinued supply of GMP-grade anti-CD137 agonist, a key TIL preparation reagent. Therefore, exploring a GMP-adherent method for expanding endogenous TILs without anti-CD137 agonist is urgent. Toward this end, we aimed to establish an anti-CD137-independent and clinically feasible TIL expansion protocol to prepare TILs from under investigated sarcoma tumors. We collected resected tumors from patients and cut tissues into fragments. We used IL-2 and T-cell activator CD3/CD28 without anti-CD137 agonist to expand nonselected TILs in 2-3 weeks, then rapidly expanded them over 2 weeks. Their phenotypes were characterized using flow cytometry. Their antitumor activity was validated in vitro using cytotoxic T lymphocyte assays measuring CD107a on the TILs and the viability of tumor cells and in vivo using an autologous patient-derived xenograft (PDX) tumor model. We successfully expanded TILs in > 90% of collected samples. TILs generated preferentially increased CD8+ T cells but suppressed CD4+ T cells. A small portion of TILs were resident memory T cells. The expanded TILs reduced autologous tumor cells by 37.5% within 24 hours. Infusion of TILs in mice bearing autologous PDX tumors strongly inhibited liposarcoma growth. FDA has approved use of this GMP-feasible protocol in our clinical trial (IND 30562). It is feasible to generate antitumor TILs using CD3/CD28 activator to replace the unavailable anti-CD137 agonist. Our study supports the further development of TIL-based therapy.
small molecules
2026-08-06 | Dedifferentiated Liposarcoma Presenting as Primary Diffuse Peritoneal Sarcomatosis: A Case Report and Literature Review.
Dedifferentiated liposarcoma (DDLPS) typically presents as a solitary retroperitoneal mass; diffuse granular and nodular peritoneal sarcomatosis as the inaugural manifestation is exceptional. We report such a case to highlight a critical diagnostic consideration: distinguishing primary sarcomatous peritoneal dissemination from the more common epithelial peritoneal carcinomatosis. A 72-year-old Chinese man with no prior abdominal surgery presented with incidentally discovered multifocal intra-abdominal masses. CT demonstrated multiple peritoneal and retroperitoneal masses with encasement of the jejunum and transmural infiltration of the descending colon, and a retroperitoneal plaque abutting the left kidney. CT-guided biopsy confirmed DDLPS via MDM2 and CDK4 amplification on fluorescence in situ hybridization. Multidisciplinary team consensus directed surgical exploration for impending dual-site bowel obstruction. Laparotomy revealed diffuse granular and nodular peritoneal deposits (Peritoneal Cancer Index 28/39); cytoreductive surgery achieved a completeness of cytoreduction score of 2. Histopathology confirmed FNCLCC Grade III DDLPS. Postoperative next-generation sequencing demonstrated high-level co-amplification of CDK4, MDM2, TSPAN31, CCND2, MDM4, and RAC1, with microsatellite stability and tumor mutational burden of 0 mutations/Mb. DDLPS can present with primary diffuse peritoneal sarcomatosis even with a retroperitoneal component. When diffuse peritoneal implants yield an epithelial-marker-negative spindle cell neoplasm on biopsy, sarcoma must be considered in the differential diagnosis and FISH for MDM2/CDK4 should be performed to avoid misdiagnosis as peritoneal carcinomatosis from gastric, colorectal, or ovarian cancer.
2026-07-23 | Transcriptional Heterogeneity in Dedifferentiated Liposarcoma Reveals Distinct Cell-Cycle Subtypes.
Dedifferentiated liposarcoma (DDLPS) is characterized by amplification of cyclin-dependent kinase 4 (CDK4). However, responses to CDK4/6 inhibition have been heterogeneous. We sought to determine whether transcriptional heterogeneity in cell-cycle regulators define biologically distinct subtypes of DDLPS that contribute to CDK4/6 inhibitor sensitivity. RNA sequencing data from The Cancer Genome Atlas sarcoma cohort (TCGA-SARC) were analyzed to identify DDLPS tumors (N = 57). Expression of key cell-cycle regulators was evaluated according to CDK4 expression to assess differences in cell-cycle regulation. Unsupervised clustering of cell-cycle regulators was performed to identify transcriptional subgroups and pathway activity across clusters was assessed. Initial comparison of tumors with high versus low CDK4 expression demonstrated differential expression of cell-cycle regulators, including increased CDK2 and CDKN2A expression in CDK4-high tumors. Unsupervised clustering identified three transcriptionally distinct subgroups characterized by patterns of CDK4 and CDK2 expression. These clusters were associated with divergent pathway activity profiles. One subgroup demonstrated high CDK4 expression with relatively low CDK2 activation and enrichment of inflammatory signaling pathways, suggesting continued reliance on the CDK4-RB axis. A second subgroup demonstrated concurrent activation of CDK4 and CDK2 alongside a proliferative transcriptional program, consistent with potential CDK2-mediated bypass of CDK4 signaling. A third subgroup demonstrated relatively low expression of both CDK4 and CDK2 with enrichment of hormone-associated signaling pathways. DDLPS tumors exhibit distinct transcriptional states within the CDK4-RB regulatory network that may influence tumor dependence on CDK4 signaling. This may impact sensitivity to CDK4/6 inhibition and explain heterogeneous outcomes.
2026-07-21 | MDM4 Amplification in Liposarcoma: A Rare Finding or an Underrecognized Pathway?
Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) is typically characterized by MDM2 and/or CDK4 amplification. However, a subset lacks these alterations, suggesting alternative oncogenic drivers. We report a patient with recurrent retroperitoneal WDLPS who developed multiple relapses over more than 25 years. Histology demonstrated a well-differentiated morphology with extensive myxoid change, without evidence of dedifferentiation. Molecular profiling using next-generation sequencing (NGS) identified MDM4 amplification, together with mutations in PIK3CA and TERT. This finding supports MDM4 as a potential alternative driver in liposarcomagenesis, possibly correlating with a more indolent clinical course. Recognition of this rare alteration is important for accurate diagnosis and may have future therapeutic implications.
2026-07-13 | Early local recurrence of well-differentiated liposarcoma of the hypopharynx in a young adult: a case report and literature review.
Well-differentiated liposarcoma (WDLPS), also termed atypical lipomatous tumor, is a low-grade malignant adipocytic neoplasm characterized by indolent growth, limited metastatic potential, and a propensity for local recurrence. Primary WDLPS arising in the hypopharyngeal region is exceptionally rare, particularly in young adults, and may clinically mimic benign submucosal lesions. We report the case of a 24-year-old man who presented with a one-month history of persistent foreign body sensation in the throat. Flexible laryngoscopy revealed a smooth submucosal mass arising from the left hypopharyngeal region, and contrast-enhanced magnetic resonance imaging demonstrated a well-circumscribed enhancing lesion without cervical lymphadenopathy. The mass was excised transorally under general anesthesia. Histopathological examination showed mature adipocytic proliferation with atypical stromal cells, and immunohistochemistry demonstrated positivity for MDM2, CDK4, CD34, and p16. Fluorescence in situ hybridization confirmed MDM2 gene amplification, establishing the diagnosis of WDLPS. Although the early postoperative course was uneventful and initial follow-up showed satisfactory mucosal healing, serial laryngoscopic examinations at 2, 2.5, and 4 months after surgery revealed early local recurrence at the surgical site. This case highlights that hypopharyngeal WDLPS can occur in young adults and may recur early even after apparently complete transoral excision. Accurate diagnosis requires integration of histopathology, MDM2/CDK4 immunohistochemistry, and molecular confirmation of MDM2 amplification. Close endoscopic and radiological surveillance is essential for early detection of local recurrence.
2026-07-13 | A Case Report: Retroperitoneal dedifferentiated liposarcoma with heterologous myogenic differentiation and testicular metastasis.
Dedifferentiated liposarcoma (DDLPS) is the most common retroperitoneal soft tissue sarcoma, characterized by MDM2 and CDK4 gene co-amplification. However, DDLPS with heterologous myogenic differentiation is extremely rare and poses a significant diagnostic challenge due to its expression of myogenic markers such as desmin, myogenin, and MyoD1, which can easily lead to misclassification as primary rhabdomyosarcoma. Testicular metastasis of DDLPS is even rarer, with only isolated case reports documented in the literature. We report a case of a 46-year-old male who presented with a large retroperitoneal mass without testicular involvement on initial imaging. He underwent en bloc resection of the retroperitoneal tumor including right nephrectomy and right hemicolectomy. Ten days postoperatively, he developed a right scrotal mass, prompting radical orchiectomy. Initial pathological evaluation suggested rhabdomyosarcoma based on desmin and MyoD1 positivity. However, subsequent expert pathological consultation with fluorescence in situ hybridization (FISH) analysis revealed MDM2 and CDK4 gene amplification in both specimens, establishing the final diagnosis of DDLPS with prominent heterologous myogenic differentiation. Postoperative chest CT demonstrated early pulmonary metastases, underscoring the aggressive nature of this tumor. This case highlights the critical importance of MDM2/CDK4 FISH testing in accurately diagnosing DDLPS with heterologous differentiation, particularly when myogenic markers are expressed, to avoid misdiagnosis and guide appropriate management.
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
2026-05-28 | 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.
2025-10-22 | Neo-inguinal reconstruction: algorithm for layered vascularized tissue coverage using plug flap following oncologic inguinal resection.
Tumors in the inguinal region are challenging to resect and reconstruct, especially when the inguinal ligament is violated. Without the shelving effect of the inguinal ligament in the setting of extensive local tissue deficit and major vessel exposure, there is an elevated risk of postoperative bowel incarceration and potential damage to the femoral neurovascular bundle. This is a retrospective case series of patients who underwent radical resection of pelvic tumors with inguinal ligament involvement. In addition to mesh placement, local flaps were layered to function as soft tissue plugs to avoid bowel herniation. Six patients with a mean age of 65.5 years were included. There were five cases of liposarcoma and one case of metastatic lung cancer. The inguinal ligament was resected in 4 patients and divided in 2 patients. The rectus abdominus was used in 3 cases and the rectus femoris in 2 cases to cover the mesh. The omentum was used in 2 patients and the sartorius in 1 patient to act as a soft tissue plug. The first inguinal ligament resection patient did not have a soft tissue plug, which resulted in incarcerated inguinal hernia. One patient with soft tissue plug developed inguinal hernia 19 months after surgery after returning to heavy labor work but did not require surgery. Patients undergoing extensive oncologic resection can benefit from neo-inguinal reconstruction by implementing a soft tissue plug between the femoral vessels and the mesh.
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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2026-04-03 | 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.
2025-10-02 | Identification of Guanine-Quadruplex-Binding Peptides from the RGG3 Domain of TLS/FUS.
Guanine quadruplexes (G4s) are non-canonical nucleic acid structures that have emerged as attractive therapeutic targets owing to their involvement in diverse biological processes. Additionally, peptides derived from G4-binding proteins provide promising platforms for selective G4 recognition. In this study, we explored the G4-binding capacity of arginine-glycine-glycine (RGG)-rich sequences derived from the RGG3 domain translocated in liposarcoma/fused in sarcoma (TLS/FUS), a known G4 RNA binding protein. In this study, we synthesized a library of overlapping 15-mer peptides and evaluated their G4-binding affinities. Among the 10 evaluated native sequences, several peptides demonstrated measurable affinities toward G4 RNA structures, with STK5-1 exhibiting the highest G4-binding affinity. Furthermore, to investigate the impact of conformational constraints on G4 recognition, we introduced (E)-methylalkene dipeptide isosteres (MADIs) into selected Gly-Gly motifs, generating a series of RGG peptidomimetics. Subsequent binding assays revealed that some of these MADI peptidomimetics exhibited enhanced affinity and selectivity compared with their unmodified counterparts. Our findings offer new insights into the sequence and structural features governing G4-binding, establishing a foundation for the further development of peptide-based G4 ligands.
2025-07-04 | Recurrent giant retroperitoneal dedifferentiated liposarcoma requiring challenging multiorgan resection: a case report.
Dedifferentiated liposarcoma is a rare, aggressive subtype of liposarcoma known for its high recurrence rate and local invasiveness. This case demonstrates the challenges in managing a rapidly recurring dedifferentiated liposarcoma and underscores the need for improved surveillance and additional treatment options. A 57-year-old non-Hispanic white male presented in November 2023 with a 2-month history of intermittent fevers, nonproductive cough, and lower abdominal discomfort. Imaging revealed a 12 cm × 12 cm × 16 cm retroperitoneal mass, confirmed to be a high-grade dedifferentiated liposarcoma. Initial surgical resection in December 2023 removed the tumor, which was densely adhered to the left kidney. Despite adjuvant chemotherapy, follow-up imaging in July 2024 showed tumor recurrence with a 15 cm × 14 cm × 21 cm multiloculated cystic mass extending from the spleen to the lower pole of the kidney, as well as a 12 cm × 6 cm × 15 cm mass inferior to the left kidney. Owing to the extensive local invasion, a second surgery in August 2024 required a left nephrectomy, splenectomy, hemicolectomy, and distal pancreatectomy. The tumor's proximity to the abdominal aorta and invasion into the psoas muscle posed significant surgical challenges, requiring careful resection. This case highlights the aggressive nature of high-grade dedifferentiated liposarcoma and its resistance to chemotherapy. Surgical resection remains the primary treatment option, but the recurrence emphasizes the need for more effective therapies. The case further illustrates the complexity of multiorgan involvement in recurrent dedifferentiated liposarcoma and the critical role of experienced oncologic surgeons in managing these cases. More research is necessary to develop alternative treatments that can better control tumor progression and improve patient outcomes.
2025-03-28 | Expression of Cancer-Testis Antigens MAGE-A1, MAGE-A4, NY-ESO-1 and PRAME in Bone and Soft Tissue Sarcomas: The Experience From a Single Center in China.
Sarcomas are a heterogeneous group of malignancies, low disease-control levels and the limited durability of responses have prompted the exploration of various novel immunotherapeutic approaches. To preliminarily explore the feasibility of cancer vaccines based on cancer testis antigen in the immunotherapy of sarcomas, we investigate the expression of Cancer/Testis Antigens (CTA) MAGE-A4, PRAME, MAGE-A1, KK-LC-1, and NY-ESO-1 in bone and soft tissue sarcomas, with the aim of assessing their potential for use in sarcoma immunotherapy and determining their expression levels in different subtypes. We employed immunohistochemistry and multiplex immunostaining microarrays (MI chips) to assess the expression of MAGE-A4, PRAME, MAGE-A1, KK-LC-1, and NY-ESO-1 in 21 cases of undifferentiated pleomorphic sarcoma (UPS), 26 cases of smooth muscle sarcoma, 28 cases of liposarcoma, 40 cases of osteosarcoma (OS), and 13 cases of chondrosarcoma. MAGE-A1 showed the highest expression in osteosarcoma (32.50%), while it was lower in liposarcoma and undifferentiated pleomorphic sarcoma (10.71% and 10.00%) and undetectable in chondrosarcoma. MAGE-A4 expression was elevated in osteosarcoma and undifferentiated pleomorphic sarcoma (40.00% and 33.00%), but lower in liposarcoma and smooth muscle sarcoma (17.00% and 33.00%). NY-ESO-1 expression was relatively low across all sarcoma subtypes. PRAME expression was highest in undifferentiated pleomorphic sarcoma (47.62%) and low in chondrosarcoma (7.69%). None of the sarcomas expressed KK-LC-1. Additionally, while there was no statistically significant correlation between CTA expression and patient age or gender, some differences related to age and gender were observed. CTA expression in bone and soft tissue sarcomas was correlated with both CTA type and sarcoma subtype, showing relatively high levels of expression in undifferentiated pleomorphic sarcoma (UPS) and osteosarcoma (OS). The poly-expression of MAGE-A4, PRAME, and MAGE-A1 across all subtypes suggests that these antigens may serve as potential targets for sarcoma-specific immunotherapy.
2025-03-27 | Anti-CD137 agonist antibody-independent and clinically feasible preparation of tumor-infiltrating lymphocytes from soft tissue sarcoma and osteosarcoma.
Tumor infiltrating lymphocytes (TILs) therapy has been proved for treatment of metastatic melanoma and is under investigation for other types of solid tumors. However, these successes are threatened by discontinued supply of GMP-grade anti-CD137 agonist, a key TIL preparation reagent. Therefore, exploring a GMP-adherent method for expanding endogenous TILs without anti-CD137 agonist is urgent. Toward this end, we aimed to establish an anti-CD137-independent and clinically feasible TIL expansion protocol to prepare TILs from under investigated sarcoma tumors. We collected resected tumors from patients and cut tissues into fragments. We used IL-2 and T-cell activator CD3/CD28 without anti-CD137 agonist to expand nonselected TILs in 2-3 weeks, then rapidly expanded them over 2 weeks. Their phenotypes were characterized using flow cytometry. Their antitumor activity was validated in vitro using cytotoxic T lymphocyte assays measuring CD107a on the TILs and the viability of tumor cells and in vivo using an autologous patient-derived xenograft (PDX) tumor model. We successfully expanded TILs in > 90% of collected samples. TILs generated preferentially increased CD8+ T cells but suppressed CD4+ T cells. A small portion of TILs were resident memory T cells. The expanded TILs reduced autologous tumor cells by 37.5% within 24 hours. Infusion of TILs in mice bearing autologous PDX tumors strongly inhibited liposarcoma growth. FDA has approved use of this GMP-feasible protocol in our clinical trial (IND 30562). It is feasible to generate antitumor TILs using CD3/CD28 activator to replace the unavailable anti-CD137 agonist. Our study supports the further development of TIL-based therapy.
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Drug Discovery Landscape
2 orphan drug designations for Liposarcoma.
2 orphan drug designations for Liposarcoma.
Drug | Therapy type | Regulator | Orphan designation | Approval | 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 | 2023-03-21 | — | Shanghai Pharma Biotherapeutics USA Inc. |
milademetan | small molecules | FDA | 2017-02-13 | — | Rain Oncology Inc. |
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