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    DRUG CLASS:

    SMARCA2 inhibitor

    Related drugs:
    2ms
    A Study of LY4050784 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=160, Recruiting, Eli Lilly and Company | Not yet recruiting --> Recruiting
    Enrollment open
    3ms
    A Study of LY4050784 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=160, Not yet recruiting, Eli Lilly and Company
    New P1 trial • Metastases
    4ms
    SMARCA2 and SMARCA4 Participate in DNA Damage Repair. (PubMed, Front Biosci (Landmark Ed))
    This study reveals SMARCA2/4 as a DNA damage repair factor for double-strand break repair.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CREBBP (CREB binding protein) • RAD51 (RAD51 Homolog A) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • RNF8 (Ring Finger Protein 8)
    |
    FHD-286
    4ms
    SMARCA4 controls state plasticity in small cell lung cancer through regulation of neuroendocrine transcription factors and REST splicing. (PubMed, J Hematol Oncol)
    This study nominates SMARCA4 as a key regulator of the NE state plasticity and defines a novel therapeutic strategy for SCLC.
    Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SRRM4 (Serine/Arginine Repetitive Matrix 4) • ASCL1 (Achaete-Scute Family BHLH Transcription Factor 1) • NEUROD1 (Neuronal Differentiation 1)
    |
    Gilotrif (afatinib) • FHD-286
    4ms
    Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer. (PubMed, Cancer Cell)
    Finally, clinical-grade pharmacologic disruption of SMARCA4/2 ATPases and BRD9 decreases POU2F3-SCLC tumor growth and increases survival in vivo. These results demonstrate mSWI/SNF-mediated governance of the POU2F3 oncogenic program and suggest mSWI/SNF inhibition as a therapeutic strategy for POU2F3-positive SCLCs.
    Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • POU2F3 (POU Class 2 Homeobox 3) • ASCL1 (Achaete-Scute Family BHLH Transcription Factor 1) • NEUROD1 (Neuronal Differentiation 1)
    |
    FHD-286
    7ms
    FHD-286 in Subjects With Metastatic Uveal Melanoma (clinicaltrials.gov)
    P1, N=76, Terminated, Foghorn Therapeutics Inc. | N=125 --> 76 | Trial completion date: Aug 2025 --> Nov 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Aug 2023 --> Nov 2023; Sponsor terminated the study for business reasons.
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Metastases
    |
    FHD-286
    9ms
    BRG1/BRM inhibitor targets AML stem cells and exerts superior preclinical efficacy combined with BET or Menin inhibitor. (PubMed, Blood)
    Compared to each drug, co-treatment with FHD-286 and BETi, MI, decitabine or venetoclax significantly reduced AML burden and improved survival, without inducing significant toxicity. These findings highlight the FHD-286-based combinations as promising therapy of AML with MLL1r or mtNPM1.
    Preclinical • Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • NPM1 (Nucleophosmin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK4 (Cyclin-dependent kinase 4) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    NPM1 mutation • MLL rearrangement • MLL rearrangement
    |
    Venclexta (venetoclax) • decitabine • FHD-286
    1year
    Notable Efficacy of Co-Treatment with FHD-286, a Dual BRG1/BRM ATP-Ase Inhibitor, and Menin or BET Inhibitor, Decitabine or Venetoclax Against AML with MLL-r or Mutant NPM1 (ASH 2023)
    BRG1 (SMARCA4) and BRM (SMARCA2) are the core ATPase within the multi-protein, ATP-dependent, chromatin remodeling BAF complexes that regulate gene transcription. Finally, co-treatment with FHD-286 and OTX015 or SNDX-5613 (oral gavage) was significantly more effective than each drug alone in reducing the AML burden and overall survival of mice engrafted with a separate PDX model of AML cells with mtNPM1 and FLT3-ITD, without significant toxicity. These findings demonstrate the pre-clinical efficacy of FHD-286-based rational combinations and underscore their promise against AML with MLL1r or mtNPM1.
    Clinical • PARP Biomarker • IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • MCL1 (Myeloid cell leukemia 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK4 (Cyclin-dependent kinase 4) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • PLK1 (Polo Like Kinase 1) • CASP3 (Caspase 3) • ITGAM (Integrin, alpha M) • BRD4 (Bromodomain Containing 4) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • CD99 (CD99 Molecule) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • HEXIM1 (HEXIM P-TEFb Complex Subunit 1) • MEF2C (Myocyte Enhancer Factor 2C) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • CLEC12A (C-Type Lectin Domain Family 12 Member A) • PBX3 (PBX Homeobox 3)
    |
    FLT3 mutation • NPM1 mutation • CD123 expression
    |
    Venclexta (venetoclax) • decitabine • revumenib (SNDX-5613) • birabresib (OTX015) • FHD-286
    1year
    Preliminary Results from a Phase 1 Dose Escalation Study of FHD-286, a Novel BRG1/BRM (SMARCA4/SMARCA2) Inhibitor, Administered As an Oral Monotherapy in Patients with Advanced Hematologic Malignancies (ASH 2023)
    Enrollment into the single-agent dose escalation phase of the study is complete. Based on nonclinical, translational, and single-agent clinical data, FHD-286 in combination with decitabine or low-dose cytarabine is being evaluated in the combination dose escalation phase of the study.
    Clinical • P1 data • Metastases
    |
    KMT2A (Lysine Methyltransferase 2A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • MECOM (MDS1 And EVI1 Complex Locus) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    cytarabine • decitabine • FHD-286
    1year
    The dual BRG1/BRM (SMARCA4/2) inhibitor FHD-286 induces functional differentiation and splicing defects in preclinical models of acute myeloid leukemia (AML). (AACR-NCI-EORTC 2023)
    No abstract available
    Preclinical
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    FHD-286
    1year
    Leukemic stem cell differentiation visible at single-cell resolution in AML patients treated with BRG1/BRM inhibitor FHD-286. (AACR-NCI-EORTC 2023)
    No abstract available
    Clinical
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    FHD-286
    1year
    FHD286 is a BRG1/BRM ATPase inhibitor showing efficacy in NSCLC models and is applicable to NSCLC patients both as a single agent treatment and in combination with current standards of care. (AACR-NCI-EORTC 2023)
    No abstract available
    Clinical • Combination therapy
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    FHD-286
    1year
    Establishing the cellular and molecular impacts of the dual BRM/BRG1 inhibitor FHD-286 on preclinical models of non-small cell lung cancer (NSCLC). (AACR-NCI-EORTC 2023)
    No abstract available
    Preclinical
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    FHD-286
    1year
    FHD-286, a potent and selective inhibitor of BRG1 and BRM, shifts metastatic uveal melanoma tumor towards a less immunosuppressive state in patient samples. (AACR-NCI-EORTC 2023)
    No abstract available
    Clinical • Metastases
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    FHD-286
    1year
    Evaluating clinical biomarkers of FHD-286, a potent and selective inhibitor of BRG1/BRM, in metastatic uveal melanoma. (AACR-NCI-EORTC 2023)
    No abstract available
    Clinical • Metastases
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    FHD-286
    over1year
    A phase I dose escalation and expansion study of FHD-286, a novel BRG1/BRM (SMARCA4/SMARCA2) inhibitor, for the treatment of metastatic uveal melanoma (ESMO 2023)
    The RP2D(s) has not yet been established. Updated dosing, safety, tolerability, PK and anti-tumor activity data will be shared at the meeting.
    P1 data • Metastases
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    FHD-286
    over1year
    FHD-286 as Monotherapy or Combination Therapy in Subjects With Advanced Hematologic Malignancies (clinicaltrials.gov)
    P1, N=50, Active, not recruiting, Foghorn Therapeutics Inc. | Suspended --> Active, not recruiting
    Enrollment closed • Combination therapy • Metastases
    |
    cytarabine • decitabine • FHD-286
    over1year
    The dual BRM/BRG1 (SMARCA2/4) inhibitor FHD-286 induces differentiation in preclinical models of AML (AACR 2023)
    Expanding on these findings, we have also demonstrated synergistic activity with multiple combination partners, including cytarabine and decitabine, in vitro. Elaboration of this in both CDX and PDX in vivo models also shows significant survival benefit in difficult to treat mutational backgrounds. Taken together, these findings suggest that FHD-286 is able to target blast progenitor populations that are heavily BRM/BRG1-dependent, and that combination with standard of care agents can achieve profound, mutationally agnostic antitumor activity in AML.
    Preclinical • IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • BCL2 (B-cell CLL/lymphoma 2) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CD34 (CD34 molecule) • ITGAM (Integrin, alpha M) • SPI1 (Spi-1 Proto-Oncogene) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    FLT3-ITD mutation • CD34 positive
    |
    cytarabine • decitabine • FHD-286
    over1year
    Pre-clinical efficacy of targeting BAF complexes through inhibition of the dual ATPases BRG1 and BRM by FHD-286 in cellular models of AML (AACR 2023)
    Additionally, co-treatment with FHD-286 and venetoclax, decitabine or OTX015, as compared to each drug alone or vehicle control, significantly reduced AML burden and improved the overall survival of the NSG mice, without inducing significant toxicity. Taken together, these findings highlight the promise of FHD-286 treatment alone and in rational combinations in exerting significant anti-AML efficacy against cellular models of AML, especially those with MLL-r, mtNPM1 or chromosome 3q26 lesions and EVI1 overexpression.
    Preclinical • IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK4 (Cyclin-dependent kinase 4) • KMT2C (Lysine Methyltransferase 2C) • NOTCH2 (Notch 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CDK6 (Cyclin-dependent kinase 6) • SPI1 (Spi-1 Proto-Oncogene) • MEF2C (Myocyte Enhancer Factor 2C) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    NPM1 mutation • MLL rearrangement • MLL rearrangement • BCL2 expression • MYC expression • NOTCH2 mutation • KMT2A expression
    |
    Venclexta (venetoclax) • decitabine • birabresib (OTX015) • FHD-286
    2years
    Pre-Clinical Efficacy of Targeting Baf Complexes through Inhibition of the Dual Atpases BRG1 and BRM By FHD-286 in Cellular Models of AML of Diverse Genetic Background (ASH 2022)
    Based on these observations, and clinical efficacy of the combination of venetoclax and decitabine/azacitidine, we determined the in vitro lethal activity of co-treatment with FHD-286 and venetoclax or decitabine against AML cell lines and PD AML cells. Additionally, co-treatment with FHD-286 and venetoclax or decitabine or OTX015, as compared to each drug alone or vehicle control, significantly reduced the AML burden and improved median and overall survival of the immune-depleted mice, without inducing significant toxicity. Taken together, these findings highlight the promise of FHD-286 treatment alone and in rational combinations in exerting significant anti-AML efficacy against cellular models of AML, especially those with MLL-r, mtNPM1 or chromosome 3q26 lesions and EVI1 overexpression.
    Preclinical • IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • KMT2C (Lysine Methyltransferase 2C) • NOTCH2 (Notch 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • ITGAM (Integrin, alpha M) • SPI1 (Spi-1 Proto-Oncogene) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    BCL2 expression • MYC expression • NOTCH2 mutation • KMT2A expression • ITGAM expression
    |
    Venclexta (venetoclax) • azacitidine • decitabine • birabresib (OTX015) • FHD-286
    2years
    Synergistic efficacy of the BRM/BRG1 ATPase inhibitor, FHD-286, and anti-PD-1 antibody in mouse syngeneic tumor models (SITC 2022)
    FHD-286 increased MHCI expression on B16F10 cells, and increases in IFNγ and Th1-type chemokine CXCL10 levels were observed in immunocompetent mice following treatment, suggesting that combinatorial activity may result from effects on both the tumor and the immune system. Conclusions FHD-286 has the potential to sensitize tumor to immune-checkpoint inhibition and represents a novel combination approach for cancer immunotherapy.
    Preclinical • PD(L)-1 Biomarker • IO biomarker
    |
    IFNG (Interferon, gamma) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    FHD-286
    over2years
    Modulation of SPI1 transcriptional program contributes to the preclinical anti-tumor activity of SMARCA4/SMARCA2 ATPase inhibitors in AML (AACR 2022)
    Using in vivo mouse models of AML, we demonstrate dose-dependent tumor growth inhibition and pharmacodynamic modulation of SPI1 target genes. Together, these data suggest that modulation of SPI1 function may, in part, provide a mechanistic basis for the clinical development of FHD-286 in AML.
    Preclinical • Late-breaking abstract
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SPI1 (Spi-1 Proto-Oncogene) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    FHD-286
    almost3years
    The molecular profile of secondary meningiomas in survivors of childhood non-central nervous system cancers (LCC 2022)
    This study examined the RIM in a cohort of patients having received similar doses of radiation for their childhood cancer. There is increased risk of radiation-induced meningioma in survivors of non-CNS cancers given ≥ 2000 cGy during childhood. To date, our findings are consistent with previously described primary and RIM mutations.
    Clinical • Tumor Mutational Burden • BRCA Biomarker
    |
    TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    NF2 mutation • MLH3 mutation
    almost3years
    Molecular features of primary hepatic undifferentiated carcinoma. (PubMed, Mod Pathol)
    Primary hepatic undifferentiated carcinoma shares clinical and genetic features with hepatocellular carcinoma but harbors progressive molecular characteristics that may initiate tumor dedifferentation. High PD-L1 expression in primary hepatic undifferentiated carcinoma may be a useful biomarker for potential immunotherapeutic strategies.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • AFP (Alpha-fetoprotein) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    PD-L1 expression • TP53 mutation • PD-L1 overexpression • IDH2 mutation • FGFR2 mutation • FGFR2 fusion • PBRM1 mutation • BAP1 mutation • AFP elevation
    almost3years
    SWI/SNF complex (SMARCA4, SMARCA2, INI1/SMARCB1) deficient colorectal carcinomas are strongly associated with microsatellite instability: An incidence study in 4508 colorectal carcinomas. (PubMed, Histopathology)
    No abstract available
    Journal • Microsatellite instability
    |
    MSI (Microsatellite instability) • 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)
    almost3years
    Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer. (PubMed, Nature)
    AU-15330 induces potent inhibition of tumour growth in xenograft models of prostate cancer and synergizes with the AR antagonist enzalutamide, even inducing disease remission in castration-resistant prostate cancer (CRPC) models without toxicity. Thus, impeding SWI/SNF-mediated enhancer accessibility represents a promising therapeutic approach for enhancer-addicted cancers.
    Journal
    |
    AR (Androgen receptor) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • FOXA1 (Forkhead Box A1) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    MYC expression
    |
    Xtandi (enzalutamide capsule)
    almost3years
    SMARCA4/BRG1-Deficient Sinonasal Carcinoma: Morphologic Spectrum of an Evolving Entity. (PubMed, Arch Pathol Lab Med)
    Inclusion of SMARCA4 in the immunohistochemical panel for diagnostic workup of all sinonasal NEC and TCS phenotypes will facilitate their early recognition. Comprehensive germline and somatic mutational analyses of these tumors are necessary for further insights into their molecular pathogenesis.
    Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • SYP (Synaptophysin)
    almost3years
    Redefine Hyperprogressive Disease During Treatment With Immune-Checkpoint Inhibitors in Patients With Gastrointestinal Cancer. (PubMed, Front Oncol)
    TGK serves as a more convenient way to reflect tumor growth acceleration compared with TGR. Genomic alterations were suggested to be associated with the occurrence of HPD.
    Clinical • Journal • Checkpoint inhibition
    |
    MSH6 (MutS homolog 6) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    almost3years
    Relationship between cellular morphology and abnormality of SWI/SNF complex subunits in pancreatic undifferentiated carcinoma. (PubMed, J Cancer Res Clin Oncol)
    Our results suggest that the abnormality of SWI/SNF complex subunits, especially ARID1A, is one of the factors behind the morphological change of UDC.
    Journal
    |
    ARID1A (AT-rich interaction domain 1A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDH1 (Cadherin 1) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • VIM (Vimentin) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    ARID1A mutation • SMARCA4 mutation • CDH1 expression • VIM expression
    almost3years
    SWI/SNF Complex-deficient Undifferentiated Carcinoma of the Gastrointestinal Tract: Clinicopathologic Study of 30 Cases With an Emphasis on Variable Morphology, Immune Features, and the Prognostic Significance of Different SMARCA4 and SMARCA2 Subunit Deficiencies. (PubMed, Am J Surg Pathol)
    Specifically, patients with loss of SMARCA4 expression had the worst overall survival (P=0.028) and disease-free survival (P=0.006) rates, compared with those with SMARCA4 expression. The loss or decreased expression of epithelial markers is thus common in SWI/SNF complex-deficient undifferentiated carcinoma of the gastrointestinal tract, and loss of SMARCA4 correlates with poor prognosis.
    Clinical • Journal
    |
    ARID1A (AT-rich interaction domain 1A) • 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)
    3years
    Cell-free DNA ultra-low-pass whole genome sequencing to distinguish malignant peripheral nerve sheath tumor (MPNST) from its benign precursor lesion: A cross-sectional study. (PubMed, PLoS Med)
    Tumor fraction levels derived from cfDNA fragment size and copy number alteration analysis of plasma cfDNA using ULP-WGS significantly correlated with MPNST tumor burden, accurately distinguished MPNST from its benign PN precursor, and dynamically correlated with treatment response. In the future, our findings could form the basis for improved early cancer detection and monitoring in high-risk cancer-predisposed populations.
    Clinical • Observational data • Journal
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    NF1 mutation
    3years
    Coexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations. (PubMed, JTO Clin Res Rep)
    Mutation and copy number variation profiles did not differ from the other TCGA tumors. Double p40+/TTF1+ lung carcinomas are aggressive and likely underrecognized non-small cell carcinomas, whose origin could reside in double-positive distal airway stem-like basal cells through either de novo-basal-like or differentiating cell mechanisms according to a model of epithelial renewal.
    Clinical • Journal • PD(L)-1 Biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • NF1 (Neurofibromin 1) • CCND1 (Cyclin D1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • IGF1R (Insulin-like growth factor 1 receptor) • RAD51B (RAD51 Paralog B) • NKX2-1 (NK2 Homeobox 1) • CCND3 (Cyclin D3) • CDK2 (Cyclin-dependent kinase 2) • KRT5 (Keratin 5) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    EGFR mutation • NF1 mutation • TP53 expression • RAD51 mutation
    3years
    A novel SMARCA2-CREM fusion: expanding the molecular spectrum of intracranial mesenchymal tumors beyond the FET genes. (PubMed, Acta Neuropathol Commun)
    Interestingly, the current case did not cluster with IMT, FET-CREB fusion-positive but rather presented histopathological (clear cell morphology with signs of malignancy), clinical (with a dismal course with several recurrences, metastases and finally the patient's death), genetic (fusion implicating the CREM gene), and epigenetic (DNA-methylation profiling) similarities with our previously reported clear cell sarcoma-like tumor of the central nervous system. Our results added data suggesting that different clinical and histomolecular tumor subtypes or grades seem to be included within the terminology "IMT, FET-CREB fusion-positive", and that further series of cases are needed to better characterize them.
    Journal
    |
    SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    3years
    SMARCA4/2 loss inhibits chemotherapy-induced apoptosis by restricting IP3R3-mediated Ca flux to mitochondria. (PubMed, Nat Commun)
    Reactivation of SMARCA2 by a histone deacetylase inhibitor rescues IP3R3 expression and enhances cisplatin response in SMARCA4/2-deficient cancer cells both in vitro and in vivo. Our findings elucidate the contribution of SMARCA4/2 to Ca-dependent apoptosis induction, which may be exploited to enhance chemotherapy response in SMARCA4/2-deficient cancers.
    Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    SMARCA4 mutation
    |
    cisplatin
    3years
    [VIRTUAL] Small Cell Carcinoma of the Ovary, Hypercalcemic Type With Tumor Infiltrating Lymphocytes (CAP 2021)
    However, the abundance of tumor infiltrating lymphocytes suggests an immunogenic tumor microenvironment, which may be a result of the transcriptional program regulated by SMARCA4. We seek to raise awareness of this highly aggressive entity with potential therapeutic implications.
    Tumor Mutational Burden • Tumor-Infiltrating Lymphocyte
    |
    TMB (Tumor Mutational Burden) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • WT1 (WT1 Transcription Factor) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • SYP (Synaptophysin)
    |
    TMB-L • SMARCA4 mutation • WT1 positive
    over3years
    Comprehensive Immunohistochemical Study of the SWI/SNF Complex Expression Status in Gastric Cancer Reveals an Adverse Prognosis of SWI/SNF Deficiency in Genomically Stable Gastric Carcinomas. (PubMed, Cancers (Basel))
    SWI/SNF aberration emerged as an independent negative prognostic factor for overall survival in genomically stable patients in analogy to TCGA. In conclusion, determination of SWI/SNF status could be suggested in routine diagnostics in genomically stable tumors to identify patients who might benefit from new therapeutic options.
    Journal
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    ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • 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) • ARID1B (AT-Rich Interaction Domain 1B) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
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    PBRM1 mutation
    over3years
    [VIRTUAL] Comprehensive genomic profiling of SMARCA2/4 alterations in Chinese pan-cancer patients (pts) identified by next generation sequencing (NGS) (ESMO 2021)
    Above all, this study reveals the genomic features of B&B in Chinese solid tumor pts by NGS. Given the continued development of B&B inhibitors, the systematic exploration of B&Bm provides profound insights of therapeutic strategies for solid tumor pts.
    Clinical • IO biomarker • Next-generation sequencing • Pan tumor
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • ARID1A (AT-rich interaction domain 1A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
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    TMB-H
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    Onco PanScan™
    over3years
    [VIRTUAL] A mutation characteristics analysis of SMARCA4defSMARCA2wt in lung cancer (ESMO 2021)
    Selective SMARCA2 degrading agents (such as ACBI1, one of PROTAC drugs) can induce the death of SMARCA4-deficient cancer cells... Our analysis indicate the medication-related mutation characteristics of SMARCA4defSMARCA2wt in lung cancer, and may contribute to medication guidance.
    PD(L)-1 Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
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    PD-L1 expression • KRAS mutation • EGFR mutation • TMB-H • PD-L1 overexpression • KRAS G12C • BRAF mutation • EGFR L858R • EGFR exon 19 deletion • MET mutation • KRAS G12 • SMARCA4 mutation
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    Onco PanScan™
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    ACBI1
    over3years
    Infrequent loss of SMARCA4, SMARCA2, and SMARCB1 expression in uterine mesenchymal tumors. (PubMed, Hum Pathol)
    SMARCA4 immunohistochemistry has potential in the diagnosis of SMARCA4-DUS with the exclusion of some tumors showing its deficiency, such as endometrial stromal sarcoma and undifferentiated carcinoma. Undifferentiated carcinoma may show an indistinguishable morphology and immunophenotype from SMARCA4-DUS, and, thus, a molecular analysis is required for their distinction in diagnostic practice.
    Journal
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    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • 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)
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    PIK3CA mutation • TP53 expression
    over3years
    The SWI/SNF complex regulates the expression of miR-222, a tumor suppressor microRNA in lung adenocarcinoma. (PubMed, Hum Mol Genet)
    Finally, we showed that the miR-222 enhancer region resides in a topologically associated domain that does not contain any cancer-related protein-coding genes, suggesting that miR-222 may be involved in exerting the tumor suppressor role of SMARCA4. Overall, this study highlights the relevant role of the SWI/SNF complex in regulating the non-coding genome, opening new insights into the pathogenesis of LUAD.
    Journal
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    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)