^
    1d
    FOXO3a deregulation in uterine smooth muscle tumors. (PubMed, Clinics (Sao Paulo))
    In summary, the outcomes of the present study suggest that the imbalance in FOXO3a within Uterine Smooth Muscle Tumors might arise from both protein phosphorylation and miRNA activity. FOXO3a could emerge as a promising therapeutic target for individuals with Unusual Leiomyomas and Leiomyosarcomas (ULM and LMS), offering novel directions for treatment strategies.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • MIR155 (MicroRNA 155) • FOXO3 (Forkhead box O3) • MIR96 (MicroRNA 96) • Let-7c (MicroRNA Let-7c)
    |
    HER-2 expression • VEGFA expression
    8d
    New treatment strategies for uterine sarcoma using secreted frizzled‑related proteins. (PubMed, Exp Ther Med)
    In conclusion, SFRP4 may suppress the viability and migration, and enhance the adhesion of sarcoma cells. These results suggested that SFRP4 could be considered as a novel therapeutic target for uterine sarcoma.
    Journal
    |
    SFRP4 (Secreted frizzled-related protein 4)
    |
    KIT expression
    14d
    Uterine myxoid leiomyosarcoma: identification of a novel PLAG1 fusion partner. (PubMed, Pathology)
    No abstract available
    Journal
    |
    PLAG1 (PLAG1 Zinc Finger)
    20d
    Nivolumab Alone or in Combination With Ipilimumab in Treating Patients With Advanced Uterine Leiomyosarcoma (clinicaltrials.gov)
    P2, N=20, Active, not recruiting, National Cancer Institute (NCI)
    Trial completion date • Combination therapy • Metastases
    |
    PD-1 (Programmed cell death 1)
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • ABP 206 (nivolumab biosimilar)
    24d
    Roles of Matrix Metalloproteinases 2 and 9 in Uterine Leiomyosarcoma. (PubMed, Anticancer Res)
    Expression levels of MMP2 and MMP9 were upregulated in malignant uLMS tumors when compared with those in benign uterine leiomyoma tumors. Increased MMP2 expression might promote uLMS invasion and migration. MMP9 overexpression might be related to uLMS occurrence; however, it protects against uLMS invasion and metastasis. MMP2 and MMP9 may be potential predictors of uLMS cell proliferation, metastasis, and prognosis. These findings could be helpful in developing new strategies for diagnosing and treating uLMS.
    Journal
    |
    MMP2 (Matrix metallopeptidase 2) • MMP9 (Matrix metallopeptidase 9)
    |
    MMP9 overexpression
    1m
    Expanding the Spectrum of NR4A3 Fusion-Positive Gynecologic Leiomyosarcomas. (PubMed, Mod Pathol)
    All cases showed high NR4A3 RNA expression levels and NOR1 (NR4A3) nuclear staining similar to salivary gland acinic cell carcinoma and a subset of extraskeletal myxoid chondrosarcomas harboring NR4A3 rearrangement. NOR1 (NR4A3) immunohistochemistry may serve as a useful diagnostic marker of NR4A3 fusion-positive gynecologic leiomyosarcomas.
    Journal
    |
    NR4A3 (Nuclear receptor subfamily 4 group A member 3) • MME (Membrane Metalloendopeptidase) • SLCO5A1 (Solute Carrier Organic Anion Transporter Family Member 5A1)
    1m
    Uterine Leiomyosarcoma Associated With Perivascular Epithelioid Cell Tumor: A Phenomenon of Differentiation/Dedifferentiation and Evidence Suggesting Cell-of-Origin. (PubMed, Am J Surg Pathol)
    We hypothesize that LMSs containing smooth muscle progenitor cells may give rise to divergent, lineage-specific PEComatous lesions through differentiation or dedifferentiation. While we do not dispute the recognition of PEComas as a distinct entity, we advocate the hypothesis that modified smooth muscle cells represent the origin of a subset of PEComas, and our case series provides evidence to suggest this theory.
    Journal
    |
    TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler) • FH (Fumarate Hydratase) • GPNMB (Glycoprotein Nmb) • CTSK (Cathepsin K)
    |
    TP53 mutation • RB1 expression • TP53 expression • TP53 R196*
    1m
    Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma. (PubMed, Clin Cancer Res)
    Compared to traditional clinicopathologic models, genomic risk stratification demonstrates superior prediction of clinical outcome in STLMS and is comparable in ULMS.
    Journal
    |
    TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler)
    |
    TP53 mutation • RB1 mutation • ATRX mutation
    2ms
    SAVE: Short Course Vaginal Cuff Brachytherapy in Treating Participants With Stage I-II Endometrial Cancer (clinicaltrials.gov)
    P3, N=188, Recruiting, University of Utah | Active, not recruiting --> Recruiting | N=108 --> 188 | Trial completion date: Sep 2024 --> Oct 2029 | Trial primary completion date: Dec 2021 --> Nov 2026
    Enrollment open • Enrollment change • Trial completion date • Trial primary completion date
    2ms
    Uterine leiomyosarcoma cell-derived extracellular vesicles induce the formation of cancer-associated fibroblasts. (PubMed, Biochim Biophys Acta Mol Basis Dis)
    miR-654-3p and miR-369-3p are highly expressed in ULMS-derived EVs, indicating that these EV-related miRNAs induce the formation of cancer-associated fibroblasts.
    Journal
    |
    ACTA2 (Actin Alpha 2 Smooth Muscle)
    2ms
    Letrozole in Uterine Leiomyosarcoma (clinicaltrials.gov)
    P2, N=40, Recruiting, GOG Foundation | Not yet recruiting --> Recruiting
    Enrollment open
    |
    ER (Estrogen receptor)
    |
    letrozole
    2ms
    Molecular profile and actionability of sarcomas with next-generation sequencing: Insights from a single institution in Brazil (Sarcoma-RC 2024)
    Despite the limitation of sample size, our study identified actionable alterations in 28% of tumor samples submitted to CGP. A high level of evidence of clinical activity according to OncoKB criteria was noted in 41% of actionable alterations. These findings underscore the importance of comprehensive genomic profiling in managing sarcomas.
    Clinical • Tumor mutational burden • Next-generation sequencing
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • CCNE1 (Cyclin E1) • MSH6 (MutS homolog 6) • CDK4 (Cyclin-dependent kinase 4) • KDM6A (Lysine Demethylase 6A) • MDM4 (The mouse double minute 4) • MUTYH (MutY homolog) • PAX3 (Paired Box 3)
    |
    TMB-H
    |
    TruSight Oncology 500 Assay
    2ms
    CDK4/MDM2 Amplification Is a Rare Targetable Genomic Event in TP53/RB1-Wildtype Uterine Leiomyosarcoma (USCAP 2024)
    Overall, in our uLMS analysis, CDK4 and/or MDM2 amplification was identified in a small subset (2%) of uLMS, the majority of which are TP53/RB1-wildtype. This may suggest that CDK4/MDM2 amplification can be an alternative tumorigenic mechanism in this distinct class of uLMS, which may have therapeutic clinical implications, including possible use of specific cyclin-dependent kinase inhibitors.
    Tumor mutational burden
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler)
    |
    TP53 mutation • MDM2 amplification • CDK4 amplification • MDM2 amplification + CDK4 amplification • RB1 wild-type • CDK4 mutation
    |
    FoundationOne® Heme CDx
    2ms
    Fumarate-Deficient Uterine Leiomyosarcoma: Molecular Confirmation of Four Cases (USCAP 2024)
    While exceedingly rarely, FH mutations may be found in uLMS. Confirmation of FH deficiency should not preclude the diagnosis of sarcoma in smooth muscle neoplasms that meet histologic criteria for malignancy.
    Clinical
    |
    TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler) • FH (Fumarate Hydratase)
    |
    TP53 mutation • MET mutation • RB1 deletion • ATRX mutation • RB deletion
    |
    FoundationOne® Heme CDx
    2ms
    CDK4/MDM2 Amplification Is a Rare Targetable Genomic Event in TP53/RB1-Wildtype Uterine Leiomyosarcoma (USCAP 2024)
    Overall, in our uLMS analysis, CDK4 and/or MDM2 amplification was identified in a small subset (2%) of uLMS, the majority of which are TP53/RB1-wildtype. This may suggest that CDK4/MDM2 amplification can be an alternative tumorigenic mechanism in this distinct class of uLMS, which may have therapeutic clinical implications, including possible use of specific cyclin-dependent kinase inhibitors.
    Tumor mutational burden
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler)
    |
    TP53 mutation • MDM2 amplification • CDK4 amplification • MDM2 amplification + CDK4 amplification • RB1 wild-type • CDK4 mutation
    |
    FoundationOne® Heme CDx
    4ms
    Cabozantinib and Temozolomide for the Treatment of Unresectable or Metastatic Leiomyosarcoma or Other Soft Tissue Sarcoma (clinicaltrials.gov)
    P2, N=72, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Dec 2023 --> Jun 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    temozolomide • Cabometyx (cabozantinib tablet)
    4ms
    Survivin-Sodium Iodide Symporter Reporter as a Non-Invasive Diagnostic Marker to Differentiate Uterine Leiomyosarcoma from Leiomyoma. (PubMed, Cells)
    Ad-Sur-NIS as a PET scan reporter is a promising imaging biomarker that can differentiate uterine LMS from LM using F18-NaBF as a radiotracer. As a new diagnostic method, the F18 NaBF PET/CT scan can provide a much-needed tool in clinical practices to effectively triage women with suspicious uterine masses and avoid unnecessary invasive interventions.
    Journal
    |
    BIRC5 (Baculoviral IAP repeat containing 5)
    4ms
    Sarcomas with RAD51B Fusions are Associated with a Heterogeneous Phenotype. (PubMed, Mod Pathol)
    Our results expand the spectrum of sarcomas with RAD51B-fusions, demonstrating variable clinical presentations, morphologic spectrum, and fusion partners. These tumors have a predilection for a uterine location, with either LMS, PEComa or undifferentiated phenotypes, and are associated with an aggressive clinical course.
    Journal
    |
    RAD51B (RAD51 Paralog B) • TSC1 (TSC complex subunit 1) • HMGA2 (High mobility group AT-hook 2)
    |
    FusionPlex® Dx
    4ms
    Testing Olaparib and Temozolomide Versus the Usual Treatment for Uterine Leiomyosarcoma After Chemotherapy Has Stopped Working (clinicaltrials.gov)
    P2/3, N=190, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | N=70 --> 190
    Enrollment open • Enrollment change • Metastases
    |
    Lynparza (olaparib) • temozolomide • Votrient (pazopanib) • Yondelis (trabectedin)
    4ms
    PReferentially Expressed Antigen in MElanoma Expression in Uterine and Ovarian Carcinosarcomas. (PubMed, Int J Gynecol Pathol)
    Our results further support PRAME overexpression in gynecologic cancers, including CS with similar expression levels in epithelial and mesenchymal components. PRAME might have a role in epithelial-mesenchymal transition in this group of cancers.
    Journal • IO biomarker
    |
    PRAME (Preferentially Expressed Antigen In Melanoma)
    |
    PRAME expression
    5ms
    Letrozole in Uterine Leiomyosarcoma (clinicaltrials.gov)
    P2, N=40, Not yet recruiting, GOG Foundation | Trial completion date: Oct 2028 --> Jun 2029 | Initiation date: Apr 2023 --> Dec 2023 | Trial primary completion date: Oct 2027 --> Jun 2028
    Trial completion date • Trial initiation date • Trial primary completion date
    |
    ER (Estrogen receptor)
    |
    letrozole
    5ms
    Ulipristal acetate, a selective progesterone receptor modulator, induces cell death via inhibition of STAT3/CCL2 signaling pathway in uterine sarcoma. (PubMed, Biomed Pharmacother)
    In vivo efficacy studies with cell line-derived xenografts and a PDX model with leiomyosarcoma, a typical uterine sarcoma, demonstrated that UPA significantly decreased tumor growth. UPA had significant anti-tumor effects in uterine sarcoma through the inhibition of STAT3/CCL2 signaling pathway and might be a potential therapeutic agent to treat this disease.
    Journal
    |
    PGR (Progesterone receptor) • CCL2 (Chemokine (C-C motif) ligand 2)
    |
    STAT3 expression • PGR expression
    5ms
    Low-grade uterine Leiomyosarcoma is highly sensitive to hormonal treatment. (PubMed, Clin Cancer Res)
    We observed a response or long-term stability rate on hormonal therapy in the 90% range; in all cases the time to relapse was significantly longer than in ULMS and in most cases the relapse was abdominal. Based on these findings, we conclude that a proportion of patients with uterine smooth muscle neoplasms actually present with a "low-grade ULMS".
    Journal
    |
    PGR (Progesterone receptor)
    6ms
    Prognostic Impact of Tumor-Infiltrating Lymphocytes, Tertiary Lymphoid Structures, and Neutrophil-to-Lymphocyte Ratio in Pulmonary Metastases from Uterine Leiomyosarcoma. (PubMed, Ann Surg Oncol)
    CD3-positive TILs, CD8-positive TILs, TLSs, and NLR are correlated with the prognosis, respectively. The combination of CD8-positive TILs or TLSs and NLR may be the indicators to predict the prognosis of patients with pulmonary metastases from uterine leiomyosarcoma.
    Retrospective data • Journal • Tumor-infiltrating lymphocyte
    |
    CD8 (cluster of differentiation 8) • FOXP3 (Forkhead Box P3) • ITGAE (Integrin Subunit Alpha E)
    |
    CD8 positive • High NLR • CD8-H
    7ms
    Chemotherapy regimen for recurrent uterine leiomyosarcoma. (PubMed, J Oncol Pharm Pract)
    It is important to comprehensively consider the patient's condition, and fully consider the efficacy, dosage, and adverse reactions of the chemotherapy regimen to determine the appropriate plan, in order to achieve the best therapeutic benefits for patients.
    Journal
    |
    gemcitabine • Focus V (anlotinib) • dacarbazine
    7ms
    Clinical Features and Prognostic Factors in Patients With Uterine Leiomyosarcoma: A Single-Center Experience. (PubMed, Cureus)
    The positive effect of adjuvant treatment on survival has not been demonstrated. Further studies are needed to investigate the effect of hormone receptor status on prognosis and new biomarkers.
    Journal
    7ms
    Pseudoprogression in patients with uterine leiomyosarcoma treated with first-line single-agent doxorubicin. (PubMed, Eur J Cancer)
    Despite the use of doxorubicin as first-line therapy for soft-tissue sarcomas for over 40 years, pseudoprogression has not been described. This retrospective study shows that pseudoprogression occurs in 19% of patients with metastatic/inoperable uterine LMS treated with first-line doxorubicin. Choi criteria were not consistently able to differentiate pseudoprogression from true progression. It is imperative that oncologists and radiologists are aware of this as symptomatically stable/improving patients may benefit from continued treatment despite initial radiological growth in tumour size.
    Journal
    |
    doxorubicin hydrochloride
    7ms
    Preclinical activity of selinexor in combination with eribulin in uterine leiomyosarcoma. (PubMed, Exp Hematol Oncol)
    In this study, we evaluated the effects of selinexor in combination with doxorubicin and eribulin in the LMS tumor model in vitro and in vivo. To our knowledge, this is the first preclinical study demonstrating the anti-cancer therapeutic potential of using a combination of selinexor and eribulin in vivo. Results from this study further warrant clinical testing a combination of chemotherapy agents with selinexor to reduce the morbidity and mortality from ULMS.
    Preclinical • Journal • Combination therapy • IO biomarker
    |
    XPO1 (Exportin 1)
    |
    doxorubicin hydrochloride • Halaven (eribulin mesylate) • Xpovio (selinexor)
    7ms
    A pan-sarcoma landscape of telomeric content shows that alterations in RAD51B and GID4 are associated with higher telomeric content. (PubMed, NPJ Genom Med)
    We further observed that sarcomas with alterations in RAD51B or GID4 were enriched in samples with high telomeric content, specifically within uterus leiomyosarcoma for RAD51B and soft tissue sarcoma (not otherwise specified, nos) for GID4, Furthermore, RAD51B and POT1 alterations were mutually exclusive with ATRX and DAXX alterations, suggestive of functional redundancy. Our results propose a role played by RAD51B and GID4 in telomere elongation in sarcomas and open research opportunities for agents aimed at targeting this critical pathway in tumorigenesis.
    Journal
    |
    ATRX (ATRX Chromatin Remodeler) • RAD51B (RAD51 Paralog B) • POT1 (Protection of telomeres 1) • DAXX (Death-domain associated protein)
    |
    FoundationOne® Heme CDx
    8ms
    Sarcoma research with cancer registry data - Data and peculiarities of Germany in the light of other countries. (PubMed, Oncol Res Treat)
    Our results correspond to the data from the literature. However, a lack of data quality and completeness hampers further meaningful analyses, especially nonspecific or missing information about morphology and stage. Compared to some other countries, a comprehensive database is presently missing in Germany. However, currently, there are important efforts and legislative initiatives to create a comprehensive database on a national level within the near future.
    Journal
    8ms
    A Rare Case of Epithelioid Leiomyosarcoma in the Uterus With ATRX Mutation in Postmenopausal Woman (CAP 2023)
    Owing to the rarity of the condition, its prognosis is still unclear. Hence, more cases with such unusual features along with long-term follow-up should be reported to assess the clinical profile of this rare neoplasm.
    Clinical
    |
    TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler) • CD99 (CD99 Molecule)
    |
    ATRX mutation
    8ms
    Phase II Study of Olaparib and Temozolomide for Advanced Uterine Leiomyosarcoma (NCI Protocol 10250). (PubMed, J Clin Oncol)
    Olaparib and temozolomide met the prespecified primary end point and provided meaningful clinical benefit in patients with advanced, pretreated uLMS.
    P2 data • Journal • PARP Biomarker • Metastases
    |
    HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A)
    |
    HRD
    |
    Lynparza (olaparib) • temozolomide
    8ms
    Next generation sequencing reveals a high prevalence of pathogenic mutations in homologous recombination DNA damage repair genes among patients with uterine sarcoma. (PubMed, Gynecol Oncol)
    Approximately 1 in 3 patients with uterine sarcoma harbor a pathogenic alteration in HR-DDR genes. Incidence is high among patients with uterine leiomyosarcoma and adenosarcoma.
    Journal • Next-generation sequencing • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • WRN (WRN RecQ Like Helicase) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCC (FA Complementation Group C)
    8ms
    Characterisation of uterine leiomyosarcomas: a single-center retrospective study of 19 tumours (ECP 2023)
    The frequent mutations in TP53, ATRX, and CDKN2A/p16 identified in our cohort support their potential as biomarkers for ULMS diagnosis and prognosis. Further studies with larger sample sizes and longer follow-up periods are needed to confirm these findings and explore the clinical utility of these biomarkers.
    Retrospective data
    |
    TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ATRX (ATRX Chromatin Remodeler)
    |
    TP53 mutation • CDKN2A mutation • ATRX mutation
    8ms
    panTRK is expressed in a variety of malignant uterine mesenchymal tumours without identifiable NTRK-associated gene fusions (ECP 2023)
    Conclusion This study supports the known conclusion that the diagnosis of a NTRK-related fusion-driven neoplasm cannot be made based solely on the immunohistochemical expression of panTRK. The significance of panTRK immunohistochemical expression in multiple different uterine mesenchymal neoplasms without NTRK-related fusions is, as of yet, not entirely clear but continues to raise questions regarding a) the exact mechanisms causing this, and b) the possible therapeutic utility of selective TRK inhibitors in the treatment of these neoplasms.
    NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK expression
    |
    VENTANA pan-TRK (EPR17341) Assay
    8ms
    GENOMIC PROFILING OF GYNAECOLOGICAL SARCOMAS: REPORT FROM THE AUSTRALIA-WIDE PRECISION ONCOLOGY PROGRAM (CTOS 2023)
    Pt with PEComa harbouring a BRCA2 mutation and high TMB (20.3 mut/Mb) was treated on a matched MoST trial of olaparib and durvalumab (ACTRN12617001000392), achieving a complete radiological response and remained progression free at 22.6 mo. Molecular characterization of GS through CGP may be prognostic and can also identify actionable alterations in small subsets of patients that can help delineate this heterogeneous group.
    Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • BRCA Biomarker
    |
    ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler) • TSC2 (TSC complex subunit 2) • TIMP3 (TIMP Metallopeptidase Inhibitor 3)
    |
    TP53 mutation • BRCA2 mutation • TMB-H • NTRK3 fusion • PTEN mutation • ALK fusion • TSC2 mutation • EML4-NTRK3 fusion
    |
    FoundationOne® CDx • TruSight Oncology 500 Assay • TruSight Tumor 170 Assay
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Vitrakvi (larotrectinib)
    8ms
    TYK2 AND MEK COMBINATION THERAPY IN MALIGNANT PERIPHERAL NERVE SHEATH TUMORS AND OTHER SOFT TISSUE SARCOMAS (CTOS 2023)
    TYK2 inhibitors decrease proliferation of MPNST cells while upregulating MEK/ERK pathway signaling in an apparent compensatory mechanism. Combining TYK2 and MEK inhibitors synergistically blocks MPNST growth in vitro and in vivo as well as other soft tissue sarcomas in vitro. These findings support the development of a combination deucravacitinib and mirdametinib phase 1/2 clinical trial in soft tissue sarcomas with an emphasis on MPNST.
    Combination therapy
    |
    NF1 (Neurofibromin 1) • TYK2 (Tyrosine Kinase 2)
    |
    mirdametinib (PD-0325901)
    8ms
    AI ANALYSIS SHOWS ENHANCED CCNG1 ONCOGENE EXPRESSION IN SARCOMA TUMORS AND SUPPORTS THE USE OF DELTAREX-G, A CCNG1 INHIBITOR, AS PLATFORM THERAPY FOR ADVANCED SARCOMA (CTOS 2023)
    Taken together, these data suggest that (1) 100% of the analyzed sarcoma tumors have enhanced CCNG1 expression, and (2) DeltaRex-G, a CCNG1 inhibitor, may be used as the platform therapy upon which targeted therapies/immunotherapies could be added. Phase 2 studies are planned using DeltaRex-G plus an mTOR inhibitor or a tyrosine kinase inhibitor, with or without immunotherapy, for advanced sarcoma.
    IO biomarker • Metastases
    |
    CCNG1 (Cyclin G1)
    8ms
    SAFETY AND PRELIMINARY BIOLOGICAL ACTIVITY OF A PHASE II TRIAL OF AUTOLOGOUS DENDRITIC CELLS VACCINATION IN SARCOMAS. (CTOS 2023)
    The first safety analysis demonstrated that autologous dendritic cell vaccine is safe and allowed the trial to continue. For the treatment efficacy evaluation more patients need to be included, nevertheless the serum cytokines evaluation showed promising signs of immune-modulating activity. In particular, all patients in which the IL-2 administrated at each cycle was related to a constantly increased IL-2 serum levels showed a better RFS.
    Clinical • P2 data
    |
    IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL2 (Interleukin 2) • IL10 (Interleukin 10) • IL1B (Interleukin 1, beta) • IL4 (Interleukin 4)
    9ms
    A RARE CASE OF ENDOBRONCHIAL METASTASIS OF UTERINE LEIOMYOSARCOMA PRESENTING AS BILATERAL SPONTANEOUS PNEUMOTHORAX (CHEST 2023)
    Given the rapid progression of the metastatic disease with persistent bilateral air leaks, she received one cycle of Doxorubicin while inpatient... Spontaneous pneumothoraces are rare but are potential complications of soft tissue sarcomas and are associated with frequent recurrence and increased mortality. Symptoms of dyspnea, chest pain, and cough should prompt evaluation for PTX in such patients. Despite EBM from endometrial sarcomas being extremely rare, it should be considered in patients who present with PTX.
    Clinical
    |
    NKX2-1 (NK2 Homeobox 1) • CDX2 (Caudal Type Homeobox 2) • GATA3 (GATA binding protein 3) • PAX8 (Paired box 8)
    |
    doxorubicin hydrochloride
    9ms
    Clinical features of uterine sarcomas presenting mainly with uterine masses: a retrospective study. (PubMed, BMC Womens Health)
    Analysis of our data showed that a large proportion of uterine sarcomas, especially uLMS and LG-ESS, present mainly with uterine masses. Ultrasound features including a large uterine mass diameter and rich hypervascularity, and with a history of myomectomy may alert clinicians in suspicion of uLMS when compared with LG-ESS.
    Retrospective data • Journal