^
    2d
    Low-Level MDM2 Amplification by FISH: An Institutional Experience With a Diagnostic Dilemma. (PubMed, Int J Surg Pathol)
    Laboratory measures and utilizing NGS assay when needed, could be implemented when encountering such problematic "low-level" MDM2 amplification specimens to avoid misdiagnosis and misuse of targeted therapy. Future studies are needed to better characterize and investigate such findings.
    Journal
    |
    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MDM2 (E3 ubiquitin protein ligase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    MDM2 amplification
    3d
    First-line Treatment of Advanced/unresectable DDLPS (clinicaltrials.gov)
    P2, N=49, Not yet recruiting, Fudan University
    New P2 trial • Combination therapy • Metastases
    |
    AiRuiKa (camrelizumab) • AiTan (rivoceranib) • pegylated liposomal doxorubicin
    6d
    The Lipid Enigma: A Case Report Highlighting Diagnostic Challenges in Adipocytic Tumors. (PubMed, Cureus)
    Infiltrating lipomas, while benign, can mimic malignant adipocytic tumors such as atypical lipomatous tumors (ALTs) and well-differentiated liposarcomas (WDLS), complicating diagnosis. This case underscores the importance of combining histopathology, immunohistochemistry (IHC), and molecular testing, particularly murine double minute clone 2 (MDM2) amplification, to distinguish between benign and malignant tumors.
    Journal
    |
    MDM2 (E3 ubiquitin protein ligase)
    7d
    PTEN pathogenic variants are associated with poor prognosis in patients with advanced soft tissue sarcoma. (PubMed, BJC Rep)
    MutPTEN vs wtPTEN was associated with worse OS in advanced STS. If confirmed, our findings could be helpful for prognostic stratification in clinical practice and for further understanding the molecular mechanisms of STS.
    Journal • Metastases
    |
    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler)
    |
    TP53 mutation • ATRX mutation
    7d
    Talimogene Laherparepvec and Radiation Therapy in Treating Patients With Newly Diagnosed Soft Tissue Sarcoma That Can Be Removed by Surgery (clinicaltrials.gov)
    P2, N=40, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • IO biomarker • Surgery
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Imlygic (talimogene laherparepvec)
    8d
    Primary Liposarcoma of the Spleen: Case Report With Review of the Literature. (PubMed, Int J Surg Pathol)
    To the best of our knowledge, this is the first description of a primary liposarcoma of the spleen reported in the literature. Due to the local recurrence risk of liposarcomas, even after R0 resection, we recommended long-term periodic follow-up.
    Review • Journal
    |
    MDM2 (E3 ubiquitin protein ligase)
    |
    MDM2 amplification
    8d
    Novel pharmacotherapies for the treatment of liposarcoma: a comprehensive update. (PubMed, Expert Opin Pharmacother)
    The search for novel agents from existing classes (tyrosine kinase inhibitors) with efficacy in liposarcoma also continues. Combination therapies as well as biomarker identification for patient selection of therapies warrant ongoing exploration.
    Review • Journal • IO biomarker
    |
    MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • CTAG1B (Cancer/testis antigen 1B)
    18d
    Primary intracranial dedifferentiated liposarcoma: An extremely rare site with unusual histopathological findings. (PubMed, Neuropathology)
    Final diagnosis of DDLS was rendered. The patient had no systemic lesions elsewhere on positron emission tomography computed tomography scan.
    Journal
    |
    MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • GFAP (Glial Fibrillary Acidic Protein) • OLIG2 (Oligodendrocyte Transcription Factor 2)
    |
    MDM2 amplification
    23d
    A Study of LN-144 or LN-145 in People With Advanced Uveal Melanoma, Undifferentiated Pleomorphic Sarcoma, or Dedifferentiated Liposarcoma (clinicaltrials.gov)
    P1, N=20, Recruiting, Memorial Sloan Kettering Cancer Center | N=10 --> 20
    Enrollment change • Metastases
    |
    Amtagvi (lifileucel) • LN-145
    25d
    Testing the Addition of Cemiplimab to Palbociclib for the Treatment of Advanced Dedifferentiated Liposarcoma (clinicaltrials.gov)
    P2, N=77, Active, not recruiting, Alliance for Clinical Trials in Oncology | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    PD-L1 (Programmed death ligand 1) • RB1 (RB Transcriptional Corepressor 1) • CDK4 (Cyclin-dependent kinase 4)
    |
    PD-L1 expression • RB1 mutation
    |
    Ibrance (palbociclib) • Libtayo (cemiplimab-rwlc)
    25d
    Recurrent Intrathoracic Liposarcoma: A Case Report and a Comprehensive Literature Review of a Rare Clinical Entity. (PubMed, Cureus)
    Long-term follow-up is crucial for managing LPSs due to their high recurrence rate. This case highlights the effectiveness of surgical intervention in recurrent intrathoracic LPSs and underlines the need for continued research into adjuvant therapies to improve patient outcomes.
    Review • Journal
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    26d
    FUS::DDIT3 Fusion Protein in the Development of Myxoid Liposarcoma and Possible Implications for Therapy. (PubMed, Biomolecules)
    Drugs that target FUS::DDIT3 and its downstream molecules for treating MLS are widely utilized in both clinical practice and experimental studies, and some of them have demonstrated promising results. This article reviews the findings of relevant research, providing an overview of the oncogenic mechanisms of the FUS::DDIT3 fusion protein in MLS, as well as recent advancements in its therapy.
    Review • Journal
    |
    FUS (FUS RNA Binding Protein) • DDIT3 (DNA-damage-inducible transcript 3)
    1m
    Study to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Untreated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma (clinicaltrials.gov)
    P2, N=7, Active, not recruiting, Adaptimmune | Trial completion date: Jul 2024 --> Jul 2025
    Trial completion date • Metastases
    |
    HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B)
    |
    HLA-A*02:01 • HLA-A*02 • CTAG1B expression • HLA-A2 positive
    |
    cyclophosphamide • fludarabine IV • letetresgene autoleucel (GSK3377794)
    1m
    Cell-cycle phase progression analysis identifies three unique phenotypes in soft tissue sarcoma. (PubMed, BMC Cancer)
    We identified three unique sarcoma cell cycle phenotypes that have prognostic significance. This performs similarly to the AJCC staging system.
    Journal
    |
    PLK1 (Polo Like Kinase 1) • MCM2 (Minichromosome maintenance complex component 2)
    1m
    Silmitasertib (CX-4945) in Combination with Chemotherapy for Relapsed Refractory Solid Tumors (clinicaltrials.gov)
    P1/2, N=114, Recruiting, Milton S. Hershey Medical Center | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy
    |
    temozolomide • irinotecan • vincristine • silmitasertib (CX-4945)
    1m
    Testing Ipilimumab and Nivolumab Combination With or Without Cabozantinib in People >= 18 Years Old With Advanced Soft Tissue Sarcoma (clinicaltrials.gov)
    P2, N=66, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting
    Enrollment open • Tumor mutational burden • IO biomarker • Metastases
    |
    TMB (Tumor Mutational Burden) • CD68 (CD68 Molecule)
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Cabometyx (cabozantinib tablet) • ABP 206 (nivolumab biosimilar)
    2ms
    Deciphering the prognostic and therapeutic significance of BAG1 and BAG2 for predicting distinct survival outcome and effects on liposarcoma. (PubMed, Sci Rep)
    The 2-gene signature model further confirmed the improved risk assessment performance of BAG1 and BAG2: high risk patients displayed poor prognosis. BAG1 and BAG2 are supposed to be potential prognostic biomarkers for LPS and have impacts on liposarcomagenesis and immune infiltration in distinctive manners, which may function as potential therapy targets (BAG1 agonists/BAG2 inhibitors) for LPS.
    Journal
    |
    TGFB1 (Transforming Growth Factor Beta 1) • BAG1 (BAG Cochaperone 1)
    2ms
    Multi-center external validation of an automated method segmenting and differentiating atypical lipomatous tumors from lipomas using radiomics and deep-learning on MRI. (PubMed, EClinicalMedicine)
    The radiomics model extended with automatic and minimally interactive segmentation methods accurately differentiated between lipomas and ALTs in two large, multi-center external cohorts, and in prospective validation, performing similar to expert radiologists, possibly limiting the need for invasive diagnostics. Hanarth fonds.
    Journal
    |
    MDM2 (E3 ubiquitin protein ligase)
    |
    MDM2 amplification
    2ms
    Gli2 Overexpression Alters the Differentiation Status of Dedifferentiated Liposarcoma Cells and Results in an Immunosuppressive Myeloid Phenotype in Orthotopic Tumors. (PubMed, bioRxiv)
    Using flow cytometry, we observed distinct changes in fat pad macrophage populations, with a particular increase in M2-like macrophages. Taken together, we find that overexpression of Gli2 in DDLPS cells alters their differentiation capacity and interactions between tumor cells and macrophages, highlighting a novel role for this developmental transcription factor in liposarcoma pathogenesis.
    Journal
    |
    GLI2 (GLI Family Zinc Finger 2)
    |
    GLI2 overexpression
    2ms
    Atypical Spindle Cell/Pleomorphic Lipomatous Tumor: A Review and Update. (PubMed, Cancers (Basel))
    This review provides an overview of the current knowledge on the clinicoradiological features, pathogenesis, histopathology, and treatment of ASCPLT. In addition, we will discuss the differential diagnosis of this new entity.
    Review • Journal
    |
    RB1 (RB Transcriptional Corepressor 1) • MDM2 (E3 ubiquitin protein ligase) • CD34 (CD34 molecule)
    |
    RB1 deletion
    2ms
    Expanded Access Protocol (EAP) for Nonconforming (NC) Afami-cel (clinicaltrials.gov)
    P=N/A, N=0, Available, Adaptimmune
    New trial
    |
    Tecelra (afamitresgene autoleucel)
    2ms
    Novel MEN1-associated retroperitoneal pleomorphic liposarcoma. (PubMed, Rare Tumors)
    We report a patient with a large retroperitoneal pleomorphic liposarcoma harboring a rare mutation of the MEN1 gene not previously reported to be associated with soft tissue sarcomas. This report expands the known spectrum of MEN1-associated cancers.
    Journal
    |
    MEN1 (Menin 1)
    2ms
    Multiple lines of evidence for disruption of nuclear lamina and nucleoporins in FUS amyotrophic lateral sclerosis. (PubMed, Brain)
    This evidence suggests that disruption of the nuclear lamina and nucleoporins is crucial for ALS pathomechanisms. Combined with patient-derived hiPSC-LMNs and autopsy samples, this mouse model might provide a more reliable understanding of ALS pathogenesis and might aid in the development of therapeutic strategies.
    Journal
    |
    FUS (FUS RNA Binding Protein)
    2ms
    Diagnosis and Treatment of Myxoid Liposarcoma. (PubMed, Curr Treat Options Oncol)
    The comprehensive treatment approach for MLS demonstrates superior local recurrence rates and survival rates compared to most soft tissue sarcomas. Current research focuses on developing effective therapies for unresectable or advanced disease based on genomic and phenotypic characteristics as well as the immune-tumor microenvironment.
    Review • Journal
    |
    FUS (FUS RNA Binding Protein) • DDIT3 (DNA-damage-inducible transcript 3)
    2ms
    Esophageal dedifferentiated liposarcoma resected by the cervical approach: a case report. (PubMed, Surg Case Rep)
    This case report highlights the use of tumor resection via the cervical approach as a good option for esophageal liposarcoma.
    Journal
    |
    CDK4 (Cyclin-dependent kinase 4)
    2ms
    The diagnosis, genetic alternation, and treatment of the primary pleomorphic liposarcoma of the femur in a rare age: Case report and literature review. (PubMed, Heliyon)
    Primary pleomorphic liposarcoma can present as sclerotic and aggressive malignant bone tumors at an early age. Excision, MAP, and MAPI chemotherapy are not enough to treat this tumor.
    Review • Journal
    |
    CREBBP (CREB binding protein) • LATS2 (Large Tumor Suppressor Kinase 2) • SMAD2 (SMAD Family Member 2)
    |
    LATS2 mutation
    2ms
    Well-differentiated inflammatory liposarcoma in the muscularis of the gallbladder. (PubMed, J Clin Ultrasound)
    We present an extremely rare case of well-differentiated inflammatory liposarcoma that occurs in the muscularis of the gallbladder, which was difficult to diagnose before surgery due to the lack of specific clinical and imaging findings. Since cyclin-dependent kinase 4 (CDK4) and murine double minute 2 (MDM2) both displayed amplification in this case, they are not only important markers for auxiliary diagnosis but also the focus of current targeted therapy.
    Journal
    |
    MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
    2ms
    Epigenetics in the formation of pathological aggregates in amyotrophic lateral sclerosis. (PubMed, Front Mol Neurosci)
    In this review, we explore the evidence that links epigenetic mechanisms with the formation of protein aggregates in ALS. We propose that a greater understanding of the role of the epigenome and how this inter-relates with the formation of pathological LLPS in ALS will provide an attractive therapeutic target.
    Review • Journal
    |
    TARDBP (TAR DNA Binding Protein) • FUS (FUS RNA Binding Protein)
    2ms
    Efficacy and Safety Study of Sindilizumab in Combination with Pipecil Targeted Therapy for First-Line Treatment of Advanced or Unresectable Liposarcoma (ChiCTR2400087517)
    P2, N=28, Not yet recruiting, Guangdong Provincial Hospital of Traditional Chinese Medicine; Guangdong Provincial Hospital of Chinese Medicine
    New P2 trial • Combination therapy • Metastases
    |
    Tyvyt (sintilimab)
    2ms
    A Phase 2, Open Label Study of PEmigatinib and REtifanlimab in Advanced Dedifferentiated LIposarcoma (PERELI) (clinicaltrials.gov)
    P2, N=33, Recruiting, Lund University Hospital | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    Pemazyre (pemigatinib) • Zynyz (retifanlimab-dlwr)
    2ms
    CD34-positive spindle cell tumour with FGFR1::TACC1 fusion: entity of uncertain behaviour (ECP 2024)
    In this particular case, the immunohistochemical and molecular results support a diagnosis of a fibroblastic/myofibroblastic tumour of uncertain behaviour. Notably, there have been no reported cases in the literature of a soft tissue tumour harboring FGFR1::TACC1 fusion as a primary occurrence in this anatomical location. The patient remains in good health without any evidence of disease recurrence at the 5-month follow-up post-surgical intervention.
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • MDM2 (E3 ubiquitin protein ligase) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • CD34 (CD34 molecule) • MME (Membrane Metalloendopeptidase) • COL1A1 (Collagen Type I Alpha 1 Chain) • NTRK (Neurotrophic receptor tyrosine kinase) • STAT6 (Signal transducer and activator of transcription 6) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex) • TACC1 (Transforming Acidic Coiled-Coil Containing Protein 1)
    |
    MDM2 amplification • FGFR1 fusion • CD34 positive
    |
    Archer® FusionPlex® Sarcoma kit • FusionPlex® Dx
    2ms
    Prospective Study Evaluating The Treatment Outcomes For Localised Recurrent, Resectable Retroperitoneal Liposarcoma (ACTRN12624000554561)
    P=N/A, N=100, Recruiting, Australia and New Zealand Sarcoma Association | Not yet recruiting --> Recruiting
    Enrollment open
    2ms
    A metabolic crosstalk between liposarcoma and muscle sustains tumor growth. (PubMed, Nat Commun)
    Repressing interleukine-6 expression, or treating liposarcoma cells with Food and Drugs Administration (FDA) approved anti-interleukine-6 monoclonal antibody, decreases de novo serine synthesis in muscle, impairs proliferation, and increases cell death in vitro and in vivo. This work reveals a metabolic crosstalk between muscle and liposarcoma tumor and identifies anti-interleukine-6 as a plausible treatment for liposarcoma patients.
    Journal
    |
    MDM2 (E3 ubiquitin protein ligase)
    2ms
    Cellular origin and clonal evolution of human dedifferentiated liposarcoma. (PubMed, Nat Commun)
    We show that tumor ASC harbor the ancestral genomic alterations of WD and DD components, suggesting that both derive from these progenitors following clonal evolution. Last, we show that DD tumor cells keep important biological properties of ASC including pluripotency and that their adipogenic properties are inhibited by a TGF-β-high immunosuppressive tumor micro-environment.
    Journal
    |
    MDM2 (E3 ubiquitin protein ligase) • TGFB1 (Transforming Growth Factor Beta 1)
    |
    MDM2 amplification
    2ms
    Diagnostic Accuracy of Immunohistochemical Expression of p16, MDM2, and CDK4 in Well-Differentiated and De-Differentiated Liposarcoma in MDM2 Fluorescent in situ Hybridisation Confirmed Cases. (PubMed, J Coll Physicians Surg Pak)
    Among all three markers, CDK4 was the most sensitive and MDM2 was the most specific marker for detecting WDLPS-DDLPS. It also showed that a combination of these three markers improves the diagnostic credibility of the immunohistochemistry in diagnosing DDLPS and WDLPS but FISH is the most reliable and confirmatory method.
    Journal
    |
    MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
    2ms
    Discovery and Characterization of Brigimadlin, a Novel and Highly Potent MDM2-p53 Antagonist Suitable for Intermittent Dose Schedules. (PubMed, Mol Cancer Ther)
    Exploratory clinical pharmacokinetic studies (NCT03449381) showed high systemic exposure and a long plasma elimination half-life in cancer patients who received oral brigimadlin. These findings support the continued clinical evaluation of brigimadlin in patients with MDM2-amplified cancers, such as dedifferentiated liposarcoma.
    Journal
    |
    MDM2 (E3 ubiquitin protein ligase)
    |
    TP53 mutation • TP53 wild-type • MDM2 amplification + TP53 wild-type
    |
    brigimadlin (BI 907828)
    2ms
    Disruptions in antigen processing and presentation machinery on sarcoma. (PubMed, Cancer Immunol Immunother)
    Sarcomas exhibit a high degree of defects in APM components, with differences among histotypes and tumoral areas. The most commonly altered APM components were HLA Class I subunit β2-microglobulin, HLA Class I subunit α (HC10), and MHC I transporting unit TAP2. The loss of APM components was prognostic of DM and OS and clinically relevant for LMS and DDLPS. This study explores sarcoma molecular mechanisms, enriching personalized therapeutic approaches.
    Journal • IO biomarker
    |
    B2M (Beta-2-microglobulin)
    3ms
    Case report: Ovarian mucinous tumor with a mural nodule of liposarcoma: a rare case. (PubMed, Front Oncol)
    This case broadens the morphological spectrum of mural nodules in ovarian mucinous tumors, deepening our knowledge of this rare morphology. Meanwhile, through high-throughput sequencing, we found no overlapping genetic evidence between the liposarcoma mural nodule and associated ovarian mucinous cystadenoma.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • ASXL1 (ASXL Transcriptional Regulator 1) • CDK4 (Cyclin-dependent kinase 4) • DDR2 (Discoidin domain receptor 2)
    3ms
    Exploiting WEE1 kinase activity as FUS::DDIT3-dependent therapeutic vulnerability in myxoid liposarcoma. (PubMed, Clin Cancer Res)
    Our preclinical study identifies WEE1-mediated replication stress tolerance as molecular vulnerability in FUS::DDIT3-driven MLS tumorigenesis that could represent a novel target for therapeutic intervention.
    Journal
    |
    CDK2 (Cyclin-dependent kinase 2) • FUS (FUS RNA Binding Protein) • WEE1 (WEE1 G2 Checkpoint Kinase) • DDIT3 (DNA-damage-inducible transcript 3)
    |
    adavosertib (AZD1775)
    3ms
    Pleomorphic Liposarcoma Cytologically Detected in Hemosiderotic Pleural Effusion: Pitfalls Mitigated by Cytologic Clues and Cellblock Immunocytochemistry. (PubMed, Diagn Cytopathol)
    Attention to certain cytologic clues mitigate pitfalls. Cellblock is a valuable diagnostic tool when integrated with relevant negative and positive immunocytochemical markers.
    Journal • Pleural effusion • Cell block
    |
    CDK4 (Cyclin-dependent kinase 4) • VIM (Vimentin) • CD68 (CD68 Molecule)
    3ms
    Immunohistochemical Evaluation of Schlafen 11 (SLFN11) Expression in Cancer in the Search of Biomarker-Informed Treatment Targets: A Study of 127 Entities Represented by 6658 Tumors. (PubMed, Am J Surg Pathol)
    Such entities may benefit from alternative treatments or strategies to overcome SLFN11 deficiency-related drug resistance. Our approach and results should serve as a foundation for future biomarker-associated clinical trials.
    Journal
    |
    SLFN11 (Schlafen Family Member 11)
    3ms
    Vulvo-vaginal stromal tumours - Case series of a rare entity from an oncology centre in India. (PubMed, Gynecol Oncol Rep)
    Therapeutically, none of the patient received adjuvant treatment, except for a single patient with angiomyxoma, who underwent chemoradiation for a synchronous cancer cervix post-surgery. This case series provides valuable insights into the clinical heterogeneity, diagnostic intricacies, and outcomes of vulvo-vaginal stromal tumours from an oncology centre in India, further contributing to a better understanding of these rare tumours.
    Journal • Stroma
    |
    CD34 (CD34 molecule) • S100P (S100 calcium binding protein P)