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:
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.
2026-07-28 | Identifying subsets of patients with retroperitoneal sarcoma who benefit from radiotherapy: an Interpretable AI reanalysis of the STRASS randomised trial.
The European Organisation for Research and Treatment of Cancer's STRASS trial, the only completed randomised study of preoperative radiotherapy in retroperitoneal sarcoma, showed no overall benefit. Its subgroup analysis has been interpreted as supporting radiotherapy for all patients with liposarcoma, whereas the STREXIT extension has been interpreted as supporting radiotherapy for well differentiated liposarcoma and low-grade or intermediate-grade dedifferentiated liposarcoma. We aimed to identify subsets of patients who might benefit from preoperative radiotherapy and to quantify this benefit in terms of abdominal recurrence. In this artificial intelligence (AI)-based reanalysis of the STRASS dataset, we trained a random survival forest model on all 266 randomly assigned patients (radiotherapy plus surgery vs surgery alone) to predict 5-year abdominal recurrence-free survival under both treatment options, based on pretreatment variables. These predictions were used to fit an optimal policy tree (OPT) that partitions patients into nodes by predicted abdominal recurrence-free survival benefit from radiotherapy. We then compared outcomes in OPT-defined subgroups, STRASS subgroups, and STREXIT subgroups through Kaplan-Meier curves, and Fine-Gray competing-risks models within STRASS. The OPT partitioned the cohort into seven subgroups; three subgroups (152 of 266 patients) were predicted to benefit from radiotherapy, and for two of these subgroups the benefit was statistically significant: patients with well differentiated liposarcoma aged 60 years or younger and patients with dedifferentiated liposarcoma who underwent curative-intent surgery. In these two subgroups combined, 3-year abdominal recurrence-free survival was 79% (95% CI 70-89) with radiotherapy versus 58% (48-72) without (hazard ratio [HR] 0·40 [95% CI 0·22-0·71], p=0·0016), and the cumulative incidence of abdominal recurrence was significantly lower with radiotherapy (17% [95% CI 9-27] vs 33% [22-45] without radiotherapy; HR 0·40, p=0·0090). Inverse probability of censoring weight-adjusted 5-year abdominal recurrence-free survival estimates showed similar absolute gains (25·6 percentage points). A Cox model found a significant radiotherapy-age interaction (p=0·012). By contrast, STRASS-defined and STREXIT-defined radiotherapy subgroups did not show significant abdominal recurrence-free survival improvement when re-evaluated within STRASS. The AI-guided partition of STRASS identified younger patients with well differentiated liposarcoma and patients with dedifferentiated liposarcoma and curative-intent surgery as subgroups in which radiotherapy appears to meaningfully improve abdominal recurrence-free survival, whereas radiotherapy strategies for all well differentiated liposarcoma and low-grade or intermediate-grade dedifferentiated liposarcoma were not supported by the randomised controlled trial data. These findings argue for a more selective use of preoperative radiotherapy in retroperitoneal sarcoma and provide a concrete basis for focused future trials, which, if successful, could substantiate these findings before these strategies become standards of care. National Cancer Institute and Memorial Sloan Kettering Cancer Center.
2026-07-23 | 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.
2026-08-06 | 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.
2026-07-28 | Identifying subsets of patients with retroperitoneal sarcoma who benefit from radiotherapy: an Interpretable AI reanalysis of the STRASS randomised trial.
The European Organisation for Research and Treatment of Cancer's STRASS trial, the only completed randomised study of preoperative radiotherapy in retroperitoneal sarcoma, showed no overall benefit. Its subgroup analysis has been interpreted as supporting radiotherapy for all patients with liposarcoma, whereas the STREXIT extension has been interpreted as supporting radiotherapy for well differentiated liposarcoma and low-grade or intermediate-grade dedifferentiated liposarcoma. We aimed to identify subsets of patients who might benefit from preoperative radiotherapy and to quantify this benefit in terms of abdominal recurrence. In this artificial intelligence (AI)-based reanalysis of the STRASS dataset, we trained a random survival forest model on all 266 randomly assigned patients (radiotherapy plus surgery vs surgery alone) to predict 5-year abdominal recurrence-free survival under both treatment options, based on pretreatment variables. These predictions were used to fit an optimal policy tree (OPT) that partitions patients into nodes by predicted abdominal recurrence-free survival benefit from radiotherapy. We then compared outcomes in OPT-defined subgroups, STRASS subgroups, and STREXIT subgroups through Kaplan-Meier curves, and Fine-Gray competing-risks models within STRASS. The OPT partitioned the cohort into seven subgroups; three subgroups (152 of 266 patients) were predicted to benefit from radiotherapy, and for two of these subgroups the benefit was statistically significant: patients with well differentiated liposarcoma aged 60 years or younger and patients with dedifferentiated liposarcoma who underwent curative-intent surgery. In these two subgroups combined, 3-year abdominal recurrence-free survival was 79% (95% CI 70-89) with radiotherapy versus 58% (48-72) without (hazard ratio [HR] 0·40 [95% CI 0·22-0·71], p=0·0016), and the cumulative incidence of abdominal recurrence was significantly lower with radiotherapy (17% [95% CI 9-27] vs 33% [22-45] without radiotherapy; HR 0·40, p=0·0090). Inverse probability of censoring weight-adjusted 5-year abdominal recurrence-free survival estimates showed similar absolute gains (25·6 percentage points). A Cox model found a significant radiotherapy-age interaction (p=0·012). By contrast, STRASS-defined and STREXIT-defined radiotherapy subgroups did not show significant abdominal recurrence-free survival improvement when re-evaluated within STRASS. The AI-guided partition of STRASS identified younger patients with well differentiated liposarcoma and patients with dedifferentiated liposarcoma and curative-intent surgery as subgroups in which radiotherapy appears to meaningfully improve abdominal recurrence-free survival, whereas radiotherapy strategies for all well differentiated liposarcoma and low-grade or intermediate-grade dedifferentiated liposarcoma were not supported by the randomised controlled trial data. These findings argue for a more selective use of preoperative radiotherapy in retroperitoneal sarcoma and provide a concrete basis for focused future trials, which, if successful, could substantiate these findings before these strategies become standards of care. National Cancer Institute and Memorial Sloan Kettering Cancer Center.
2026-07-23 | 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.
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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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