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CANCER:

Synovial Sarcoma

5d
Immunological differences between monophasic and biphasic synovial sarcoma with implications for immunotherapy. (PubMed, Cancer Immunol Immunother)
Together these data demonstrate that biphasic synovial sarcoma is immunologically different from monophasic synovial sarcoma and might be more susceptible to immunotherapies such as adoptive T-cell therapy. Finally, T-cell infiltration in primary synovial sarcoma was associated with prolonged overall survival of patients which suggests that intratumoral T cells may demonstrate anti-tumor activity.
Journal
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CD163 (CD163 Molecule) • CD68 (CD68 Molecule)
5d
SS18-SSX drives TYK2 expression to activate STAT3/Bcl2 axis, facilitating apoptosis evasion and advancing synovial sarcoma progression. (PubMed, Cell Biol Toxicol)
Thus, the TYK2/STAT3/Bcl2 axis is a crucial mechanism through which SS18-SSX mediates apoptosis evasion in SS cells. In conclusion, our findings contribute to understanding how SS18-SSX-driven TYK2 expression mediates apoptosis evasion mechanisms and propose targeting TYK2 as a strategy to induce apoptosis in SS.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • TYK2 (Tyrosine Kinase 2) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
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BCL2 expression
7d
Histologic and immunologic factors associated with response to immune checkpoint inhibitors in advanced sarcoma. (PubMed, Clin Cancer Res)
ORR and PFS were highly variable across sarcoma histologic subtype. In this large analysis, KS, ASPS, AS, MFS, and UPS demonstrated the highest ORR and longest PFS while osteosarcoma, SS, and LPS had the lowest ORR and shortest PFS. PD-L1 expression was also associated with increased ORR. Our findings provide further insight into understanding the sarcoma histologic and immunologic factors that correspond with response to ICIs.
Journal • Checkpoint inhibition • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden)
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PD-L1 expression
8d
ROOT: The Registry of Oncology Outcomes Associated with Testing and Treatment (clinicaltrials.gov)
P=N/A, N=167, Completed, Taproot Health | Recruiting --> Completed | N=100000 --> 167 | Trial completion date: Oct 2031 --> Oct 2024 | Trial primary completion date: Oct 2029 --> Oct 2024
Trial completion • Enrollment change • Trial completion date • Trial primary completion date
8d
Phase classification • Metastases
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SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1)
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CFT8634
15d
A Phase 1 Study of FHD-609, a Heterobifunctional Degrader of Bromodomain-Containing Protein 9, in Patients With Advanced Synovial Sarcoma or SMARCB1-Deficient Tumors. (PubMed, Clin Cancer Res)
FHD-609 showed dose-dependent increases in systemic FHD-609 exposure and pharmacodynamic response profiles. The MTDs were identified (40 mg BIW/80 mg QW) and preliminary clinical activity was observed. Future studies of BRD9 degraders will require strict cardiac monitoring given the QTc prolongation observed in this study.
P1 data • Journal • Metastases
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SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1)
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FHD-609
18d
Primary intracranial DICER1-mutant sarcoma: a clinicopathological analysis of seven cases (PubMed, Zhonghua Bing Li Xue Za Zhi)
Primary intracranial DICER1-mutant sarcoma is a rare tumor. Understanding its morphological characteristics, immunohistochemical and molecular markers and differential diagnosis is crucial to avoid misdiagnosis and to improve diagnostic accuracy of this tumor.
Retrospective data • Journal
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TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler) • DICER1 (Dicer 1 Ribonuclease III) • SALL4 (Spalt Like Transcription Factor 4)
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TP53 mutation
23d
Efficacy of CBP/p300 Dual Inhibitors against De-repression of KREMEN2 in cBAF-Deficient Cancers. (PubMed, Cancer Res Commun)
Furthermore, treatment with CBP/p300 dual inhibitor suppressed the growth of xenografts derived from SMARCA4/SMARCA2-deficient and SS18-SSX fusion cancer cells, resulting from repression of KREMEN2 and induction of apoptosis. Thus, CBP/p300 dual inhibitors could be promising for SMARCA4/SMARCA2-deficient lung cancer and SS18-SSX fusion synovial sarcoma, which are entirely deficient in the cBAF complex.
Journal
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SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
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SS18-SSX fusion
1m
EZH2 inhibition sensitizes retinoic acid-driven senescence in synovial sarcoma. (PubMed, Cell Death Dis)
Exposure to GSK343 or ATRA results in inhibition of cell proliferation and induction of cellular senescence, where GSK343 shows a dominant effect. The Figure was created with Biorender.com.
Journal
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RARA (Retinoic Acid Receptor Alpha) • PRAME (Preferentially Expressed Antigen In Melanoma) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
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PRAME expression • SS18-SSX fusion
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GSK343
1m
A Comprehensive Review of TRPS1 as a Diagnostic Immunohistochemical Marker for Primary Breast Carcinoma: Latest Insights and Diagnostic Pitfalls. (PubMed, Cancers (Basel))
While TRPS1 remains a highly sensible immunohistochemical marker for confirming breast primary lesions, pathologists should be aware of its low specificity and incorporate complementary diagnostic methods in order to ensure accurate clinical management. Further research should focus on elucidating the molecular pathways regulating TRPS1 expression in various tumor types, which may better define its clinical utility.
Review • Journal • IO Complimentary diagnostic
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SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex) • TRPS1 (Transcriptional Repressor GATA Binding 1)
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SS18-SSX fusion
1m
Advances of SS18-SSX fusion gene in synovial sarcoma: Emerging novel functions and therapeutic potentials. (PubMed, Biochim Biophys Acta Rev Cancer)
Treatment of synovial sarcoma typically comprises local surgery, radiotherapy and chemotherapy, while novel managements such as immunotherapy, targeted therapies and epigenetic modifiers are explored. This review focuses on the recent studies of SS18-SSX fusion gene, epigenetic landscape, signaling pathways, diagnostic techniques, and relevant therapeutic advances, aiming to inhibit the oncogenic processes and improve outcomes for patients with synovial sarcoma.
Review • Journal • IO biomarker
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SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
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SS18-SSX fusion
1m
SSX2IP promotes cell proliferation and migration in breast cancer by regulating FANCI. (PubMed, Cell Biol Int)
Furthermore, FANCI overexpression partially reversed the effects of SSX2IP knockdown on cell proliferation and metastasis. In summary, our findings revealed that SSX2IP contributes to the progression of breast cancer by regulating FANCI, hinting at its potential as a novel biomarker and therapeutic target for the treatment of breast cancer.
Journal
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FANCI (FA Complementation Group I)
1m
Patterns of expression of VEGFR2, PDGFRs and c-Kit in pediatric patients with high grade non-rhabdomyosarcoma soft tissue sarcoma. (PubMed, Front Oncol)
Our findings indicated that tyrosine kinase receptors are upregulated in NRSTS and exhibited a distinct expression pattern within various subgroups. High expression of VEGFR2 and PDGFRα significantly correlated with reduced survival and may guide targeted therapy approaches for this poor prognosis group of patients.
Journal
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KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • KDR (Kinase insert domain receptor) • PDGFRB (Platelet Derived Growth Factor Receptor Beta)
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KDR overexpression • KDR expression • KIT expression • PDGFRA expression
2ms
Condensate remodeling reorganizes innate SS18 in synovial sarcomagenesis. (PubMed, Oncogenesis)
Consequently, this leads to the downregulation of tumor suppressor genes occupied by SS18 physiologically, like CAV1 and DAB2. These results reveal the underlying mechanism of genomic disorder and tumorigenesis caused by the remodeling of oncoprotein SS18-SSX1 condensates at the macroscopic level.
Journal
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CAV1 (Caveolin 1) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex) • SSX1 (SSX Family Member 1)
2ms
Genetic and Molecular Heterogeneity of Synovial Sarcoma and Associated Challenges in Therapy. (PubMed, Cells)
Novel approaches to treating synovial sarcoma include immune-based therapies (such as TCR-T cell therapy to NY-ESO-1, MAGE4, PRAME or using immune checkpoint inhibitors), epigenetic modifiers (HDAC inhibitors, EZH2 inhibitors, BRD disruptors), as well as novel or repurposed receptor tyrosine kinase inhibitors. In the presented review, we aimed to summarize the genetic and epigenetic landscape of SS as well as to find out the potential niches for the development of novel diagnostics and therapies.
Review • Journal
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CTAG1B (Cancer/testis antigen 1B) • MAGEA4 (Melanoma antigen family A, 4) • PRAME (Preferentially Expressed Antigen In Melanoma) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
2ms
SS18-SSX Expression and Clinicopathologic Profiles in a Contemporary Cohort of Primary Paratesticular Synovial Sarcoma: A Series of Fourteen Patients. (PubMed, Am J Surg Pathol)
SS18-SSX-positive staining may be used as a surrogate for FISH assay in a resource-limited setting where molecular assay is not available. Furthermore, IHC has a fairly shorter turn-around-time, is less complex, and of low cost.
Journal
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SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex) • SSX1 (SSX Family Member 1)
2ms
Trial completion date • Metastases
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HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B)
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HLA-A*02:01 • HLA-A*02 • CTAG1B expression • HLA-A2 positive
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cyclophosphamide • fludarabine IV • letetresgene autoleucel (GSK3377794)
2ms
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
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PLK1 (Polo Like Kinase 1) • MCM2 (Minichromosome maintenance complex component 2)
2ms
Afamitresgene Autoleucel: First Approval. (PubMed, Mol Diagn Ther)
In August 2024, afamitresgene autoleucel was approved in the USA under accelerated approval for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P or -A*02:06P positive and whose tumour expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices. This article summarizes the milestones in the development of afamitresgene autoleucel leading to this first approval for the treatment of advanced synovial sarcoma.
Review • Journal • IO Companion diagnostic
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HLA-A (Major Histocompatibility Complex, Class I, A) • MAGEA4 (Melanoma antigen family A, 4)
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HLA-A*02
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Tecelra (afamitresgene autoleucel)
3ms
SUMO2 Inhibition Reverses Aberrant Epigenetic Rewiring Driven by Synovial Sarcoma Fusion Oncoproteins and Impairs Sarcomagenesis. (PubMed, bioRxiv)
Our study identifies SUMO2 as a selective dependency in synovial sarcoma. We demonstrate that the SUMO2/3 inhibitor TAK-981 impairs sarcomagenesis and reverses the SS18-SSX fusion-driven oncotranscriptome. Our study indicates that SUMO2 inhibition may be an attractive therapeutic option in synovial sarcoma.
Journal
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SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
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SS18-SSX fusion
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subasumstat (TAK-981)
3ms
Study of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients With Solid Tumors (clinicaltrials.gov)
P1, N=22, Active, not recruiting, University Health Network, Toronto | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025
Trial completion date • Trial primary completion date
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HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B)
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HLA-A*02 • CTAG1B expression
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cyclophosphamide • fludarabine IV • mipetresgene autoleucel (TBI-1301)
3ms
Nuclear DUX4 immunohistochemistry is a highly sensitive and specific marker for the presence of CIC::DUX4 fusion in CIC-rearranged sarcomas: a study of 48 molecularly confirmed cases. (PubMed, Histopathology)
DUX4 IHC is a highly sensitive and specific surrogate marker for the presence of CIC::DUX4 fusion, demonstrating its utility in establishing a diagnosis of CRS.
Journal
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SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • DUX4 (Double Homeobox 4)
3ms
New P1/2 trial
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zoledronic acid
3ms
New trial
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Tecelra (afamitresgene autoleucel)
3ms
Expression of POU2F3 Transcription Factor and POU2AF2, POU2F3 Coactivator, in Tuft Cell-like Carcinoma and Other Tumors. (PubMed, Am J Surg Pathol)
POU2F3 expression is a highly sensitive but nonspecific indicator of tuft cell differentiation. Co-expression of POU2F3 and POU2AF2 appears to be a more specific marker, although it may not pinpoint tumors driven by the POU2F3-POU2AF3 complex.
Journal
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POU2F3 (POU Class 2 Homeobox 3)
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POU2F3 expression
3ms
BRD9 promotes the progression of gallbladder cancer via CST1 upregulation and interaction with FOXP1 through the PI3K/AKT pathway and represents a therapeutic target. (PubMed, Gene Ther)
The transcription factor FOXP1 was found to interact with BRD9 to regulate CST1 expression. Collectively, these results suggest that BRD9 may be a promising biomarker and therapeutic target for GBC.
Journal
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FOXP1 (Forkhead Box P1)
3ms
AOH1996 for the Treatment of Refractory Solid Tumors (clinicaltrials.gov)
P1, N=92, Recruiting, City of Hope Medical Center | Active, not recruiting --> Recruiting | Trial completion date: Sep 2024 --> Jan 2026 | Trial primary completion date: Sep 2024 --> Jan 2026
Enrollment open • Trial completion date • Trial primary completion date
3ms
The BCOR-rearranged sarcoma involving the lung: Diagnosis with clinical outcome and literature review. (PubMed, Indian J Pathol Microbiol)
An exact confirmation by molecular testing has treatment-associated implications. A review of similar reported cases is presented herewith.
Clinical data • Review • Journal
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BCOR (BCL6 Corepressor)
3ms
Synovial sarcoms presenting atypical FISH positive pattern with loss of green signal. Molecular characteristics of 2 new cases and systematic review of the literature (ECP 2024)
Atypical SS18-break apart FISH pattern with loss of green signal should be interpreted as a peculiar unbalanced rearrangement of the SS18 gene and subsequent SS18-SSX fusion (IHC or/and NGS) test should be recommended in such cases. Reseach are partially supported by grant of the The National Centre for Research and Development no. GOSPOSTRATEG-VI/0016/2021.
Clinical • Review
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SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex) • SSX1 (SSX Family Member 1)
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SS18-SSX fusion
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Archer® FusionPlex® Sarcoma kit • FusionPlex® Dx
3ms
Challenging presentations of synovial sarcomas: shedding light on the uncommon (ECP 2024)
Our cases on atypical presentations of SS shows unusual morphological, immunophenotype, and molecular features. We consider it relevant to include SS as a differential diagnosis when faced with pseudo-vascular/alveolar patterns. Even in cases with more typical morphology of SS, there is a possibility of finding negative results in either IHC or FISH techniques due to cryptic or complex rearrangement.
SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex) • SSX1 (SSX Family Member 1)
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Archer® FusionPlex® Sarcoma kit
4ms
Molecular Profiling Defines Three Subtypes of Synovial Sarcoma. (PubMed, Adv Sci (Weinh))
KRT8 was identified as a key component for epithelial differentiation in biphasic tumors, potentially controlled by OVOL1 regulation. Our findings explain the histological grounds for SS classification and indicate that a significantly larger proportion of patients have high risk tumors (corresponding to SS subtype I) than previously believed.
Journal
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SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
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SS18-SSX fusion
4ms
Mitoregulin modulates inflammation in osteoarthritis: Insights from synovial transcriptomics and cellular studies. (PubMed, Biochem Biophys Res Commun)
We found that MTLN overexpression or knockout respectively decreased or increased expression of the inflammation-associated genes, including IL-6, IL-8, and TNF-α. Thus, high levels of MTLN in osteoarthritis may protect tissues against excessive inflammation, thereby offering therapeutic potentials.
Journal
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL8 (Chemokine (C-X-C motif) ligand 8)
4ms
Brief Communication on MAGE-A4 and Coexpression of Cancer Testis Antigens in Metastatic Synovial Sarcomas: Considerations for Development of Immunotherapeutics. (PubMed, J Immunother)
Among MAGE-As, MAGE-A4 had the highest prevalence (65%), followed by MAGE-A10 (15%) and MAGE-A9 (13%)...Complementary immunohistochemical analyses were used to establish the positive correlation between RNA and protein expression for MAGE-A4 and NY-ESO-1. These data inform the strategy for optimal coverage of the SyS patient population with T-cell therapies, offering patients with SyS new options for single or combined second lines of treatment.
Journal • IO biomarker • Metastases
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CTAG1B (Cancer/testis antigen 1B) • MAGEA4 (Melanoma antigen family A, 4) • PRAME (Preferentially Expressed Antigen In Melanoma)
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MAGEA4 expression
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ADP-A2M10
4ms
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
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SLFN11 (Schlafen Family Member 11)
4ms
Establishment and characterization of NCC-SS6-C1: a novel patient-derived cell line of synovial sarcoma. (PubMed, Hum Cell)
Additionally, we confirmed that this cell line was useful for evaluating the efficacy of anticancer drugs. Our results suggest that NCC-SS6-C1 is a useful tool for basic and pre-clinical studies of SS.
Preclinical • Journal
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SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex) • SSX1 (SSX Family Member 1)
4ms
Investigating the prognostic impact of NY-ESO-1 expression and HLA subtypes in metastatic synovial sarcoma. (PubMed, ESMO Open)
The primary tumor cohort showed no association between NY-ESO-1 expression and OS (including stratification by HLA-A∗02 subtype and treatment line), when adjusting for important prognostic factors, possibly due to small sample sizes.
Journal • Metastases
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HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B)
4ms
Rare mediastinal small round cell melanoma with synovial sarcoma-like immunophenotype: A potential diagnostic pitfall. (PubMed, Pathol Res Pract)
NGS results revealed NRAS and CDKN2A mutations and absence of fusions, resulting in a new review of the histologic material with a broader immunohistochemical panel, finding strong positivity to melanic antibodies. This case is an illustrative example of a malignant melanoma with small round cell morphology showing aberrant expression of CD99, BCL2, TLE1 and SS18-SSX antibodies exposing a potentially hazardous pitfall highlighting the importance of a wide differential diagnosis and the role of confirmational studies with molecular tests.
Journal • IO biomarker
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NRAS (Neuroblastoma RAS viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CD99 (CD99 Molecule) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
5ms
Discovery of CW-3308 as a Potent, Selective, and Orally Efficacious PROTAC Degrader of BRD9. (PubMed, J Med Chem)
Oral administration effectively inhibited HS-SY-II xenograft tumor growth in mice. CW-3308 is a promising lead compound for further optimization and extensive evaluation for the treatment of synovial sarcoma, rhabdoid tumor, and other BRD9-dependent human diseases.
Journal
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CRBN (Cereblon) • BRD4 (Bromodomain Containing 4)
5ms
FDA Grants Thermo Fisher Scientific SeCore HLA Typing Kit 510(k) Clearance for Use as Companion Diagnostic with a T-Cell Receptor Therapy for Synovial Sarcoma (Businesswire)
"Thermo Fisher Scientific Inc...announced that its SeCore CDx HLA A Sequencing System has been granted 510(k) clearance by the United States Food and Drug Administration (FDA) for use as a companion diagnostic with TECELRA (afamitresgene autoleucel), Adaptimmune’s newly approved T-cell receptor (TCR) therapy for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices. Synovial sarcoma is a rare, soft tissue cancer that most commonly impacts young adults."
FDA event
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SeCore CDx HLA Sequencing System
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Tecelra (afamitresgene autoleucel)
5ms
Agilent Receives FDA Approval for MAGE-A4 IHC 1F9 pharmDx as a Diagnostic Tool for Use with Newly Approved TCR T-Cell Therapy (Businesswire)
"Agilent Technologies Inc...announced that it has received FDA approval for the use of MAGE-A4 IHC 1F9 pharmDx (SK032) as a diagnostic tool to aid in identifying patients with synovial sarcoma who may be eligible for treatment with TECELRA (afamitresgene autoleucel, also known as afami-cel or ADP-A2M4), a MAGE-A4-directed engineered TCR T-Cell therapy."
FDA event
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MAGE-A4 IHC 1F9 pharmDx (SK032)
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Tecelra (afamitresgene autoleucel)
5ms
The Combined Immunohistochemical Expression of GLI1 and BCOR in Synovial Sarcomas for the Identification of Three Risk Groups and Their Prognostic Outcomes: A Study of 52 Patients. (PubMed, Int J Mol Sci)
Moreover, these markers could represent therapeutic targets in advanced stages. However, further, larger series of SSs and molecular studies are necessary to corroborate our present findings.
Journal
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BCOR (BCL6 Corepressor) • GLI1 (GLI Family Zinc Finger 1) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex) • TRPS1 (Transcriptional Repressor GATA Binding 1)