^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    DRUG CLASS:

    SMARCA4 inhibitor

    Related drugs:
    5ms
    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
    5ms
    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
    5ms
    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
    8ms
    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
    10ms
    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
    10ms
    Efficacy of immune checkpoint inhibitors in SMARCA4-deficient and TP53 mutant undifferentiated lung cancer. (PubMed, Medicine (Baltimore))
    However, hyperprogressive disease by ICIs may also happen for such patients. The mutation types of TP53 might play a role during the exposure of ICIs, however, need further identification in basic experiments.
    Journal • Checkpoint inhibition • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • NCAM1 (Neural cell adhesion molecule 1) • NKX2-1 (NK2 Homeobox 1) • TP63 (Tumor protein 63) • NAPSA (Napsin A Aspartic Peptidase)
    |
    TP53 mutation • TMB-L
    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 • Revuforj (revumenib) • 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
    over1year
    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
    over1year
    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
    over1year
    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
    over1year
    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
    over1year
    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
    over1year
    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
    almost2years
    The SMARCA4 mutation facilitates chromatin remodeling and confers PRMT1/SMARCA4 inhibitors sensitivity in colorectal cancer. (PubMed, NPJ Precis Oncol)
    Together, our findings show that SMARCA4-R1157W is a critical activating mutation, which accelerates CRC progression through facilitating chromatin recruitment and remodeling. Our results suggest a potential precision therapeutic strategy for the treatment of CRC patients carrying the SMARCA4 mutation.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • PRMT1 (Protein Arginine Methyltransferase 1)
    |
    EGFR mutation • EGFR expression • SMARCA4 mutation
    almost2years
    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
    almost2years
    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
    almost2years
    Targetable Brg1-CXCL14 axis contributes to alcoholic liver injury by driving neutrophil trafficking. (PubMed, EMBO Mol Med)
    Finally, a positive correlation between Brg1 expression, CXCL14 expression, and neutrophil infiltration was detected in ALD patients. In conclusion, our data provide proof-of-concept for targeting the Brg1-CXCL14 axis in ALD intervention.
    Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    2years
    Epigenetic Rewiring Underlies SMARCA4-Dependent Maintenance of Progenitor State in Pediatric H3K27M Diffuse Midline Glioma. (PubMed, Cancer Discov)
    Inhibiting BRG1 ATPase represents a potential therapeutic strategy for pediatric H3K27M DMG. See related article by Panditharatna et al., p. 2880 (5) See related article by Mo et al., p. 2906 (4) .
    Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SOX10 (SRY-Box 10)
    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
    Efficacy of Immune Checkpoint Inhibitors in SMARCA4-Deficient Thoracic Tumor. (PubMed, Clin Lung Cancer)
    PD-1/PD-L1 inhibitors showed promising results in the treatment of SMARCA4-deficient tumor. Further studies, especially on patient selection and combination therapy, are needed.
    Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    SMARCA4 mutation
    almost3years
    Preclinical characterization of PRT3789, a potent and selective SMARCA2 targeted degrader (AACR 2022)
    In subcutaneous cell-line derived xenograft (CDX) models of NSCLC, administration of PRT3789 demonstrated significant dose-related inhibition of SMARCA4-deleted NSCLC growth at tolerated doses, but no effect on the growth of SMARCA4 WT cancers. In summary, consistent with our previous validation studies and genomic perturbation analyses, our potent and selective SMARCA2 targeted degrader PRT3789 induces strong synthetic lethality in SMARCA4-deleted cancers in vitro and in vivo.
    Preclinical
    |
    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 • SMARCA4 deletion
    |
    PRT3789
    almost3years
    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
    Novel structural-related analogs of PFI-3 (SRAPs) that target the BRG1 catalytic subunit of the SWI/SNF complex increase the activity of temozolomide in glioblastoma cells. (PubMed, Bioorg Med Chem)
    In the present study we designed and synthesized Structurally Related Analogs of PFI-3 (SRAPs) and tested their bioactivity in vitro. Among of the SRAPs, 9f and 11d show better efficacy than PFI-3 in sensitizing GBM cells to the antiproliferative and cell death inducing effects of temozolomide in vitro, as well as enhancing the inhibitor effect of temozolomide on the growth of subcutaneous GBM tumors.
    Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    temozolomide
    almost3years
    BRG1 and NPM-ALK Are Co-Regulated in Anaplastic Large-Cell Lymphoma; BRG1 Is a Potential Therapeutic Target in ALCL. (PubMed, Cancers (Basel))
    Furthermore, we show that BRG1 drives a transcriptional programme associated with cell cycle progression. In turn, inhibition of BRG1 expression with specific shRNA decreases cell viability, suggesting that it may represent a key therapeutic target for the treatment of ALCL.
    Journal • IO biomarker
    |
    ALK (Anaplastic lymphoma kinase) • NPM1 (Nucleophosmin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    ALK translocation
    almost3years
    BAF complexes drive proliferation and block myogenic differentiation in fusion-positive rhabdomyosarcoma. (PubMed, Nat Commun)
    Phenotypically, interference with mSWI/SNF complex function induces transcriptional activation of the skeletal muscle differentiation program associated with MYCN enhancer invasion at myogenic target genes, which is recapitulated by BRG1 targeting compounds. We conclude that inhibition of BRG1 overcomes the differentiation blockade of FP-RMS cells and may provide a therapeutic strategy for this lethal childhood tumor.
    Journal
    |
    MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • PAX3 (Paired Box 3)
    3years
    Exquisite Sensitivity to Dual BRG1/BRM ATPase Inhibitors Reveals Broad SWI/SNF Dependencies in Acute Myeloid Leukemia. (PubMed, Mol Cancer Res)
    Overall, small molecule inhibition of BRG1/BRM induced common transcriptional responses across leukemia models resulting in a spectrum of cellular phenotypes. Implications: Our studies reveal the breadth of SWI/SNF dependency in leukemia and support targeting SWI/SNF catalytic function as a potential therapeutic strategy in AML.
    Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    3years
    SMARCA4: Implications of an altered chromatin-remodeling gene for cancer development and therapy. (PubMed, Mol Cancer Ther)
    Importantly, immune checkpoint blockade has shown remarkable, albeit anecdotal, responses in SCCOHT. Additionally, there is ongoing research into BET, EZH2, HDAC, CDK4/6, and FGFR inhibitors, as well as agents that might induce synthetic lethality via DNA damage repair impairment (ATR inhibitors and platinum chemotherapy), or via the exploitation of mitochondrial oxidative phosphorylation inhibitors or AURKA inhibitors, in SMARCA4¬-aberrant cancers.
    Review • Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    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
    |
    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)
    |
    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
    |
    Onco PanScan™
    |
    ACBI1
    over3years
    Phosphorylation of Ser1452 on BRG1 inhibits the function of the SWI/SNF complex in chromatin activation. (PubMed, J Proteomics)
    In brg1-SD cells, we also detected downregulation of various cancer-related proteins (e.g., EGFR and MET) as well as decreased migration, proliferation, and sensitivity to taxanes and oxaliplatin...In phosphorylation-mimic mutant, significant decrease of various cancer-related proteins as well as migration, proliferation, and sensitivity to specific antitumor agents were detected. Our results reveal that BRG1 phosphorylation drives tumor malignancy by inhibiting the functions of SWI/SNF complex in chromatin activation, thereby promoting expression of various cancer-related proteins.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    oxaliplatin
    over3years
    BET inhibitor suppresses migration of human hepatocellular carcinoma by inhibiting SMARCA4. (PubMed, Sci Rep)
    Bromodomain and extraterminal (BET) inhibitors, such as JQ1 and OTX-015, inhibit BET protein binding to acetylated residues in histones. Furthermore, knockdown of SMARCA4 gene expression by siRNA treatment significantly reduced cell migration and the expression of migration-related genes. In summary, our results indicated that BET inhibitor treatment in HCC cell lines reduces cell migration through the downregulation of SMARCA4.
    Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • BRD4 (Bromodomain Containing 4) • SSTR5 (Somatostatin Receptor 5)
    |
    JQ-1 • birabresib (OTX015)
    over3years
    PRMT1-mediated H4R3me2a recruits SMARCA4 to promote colorectal cancer progression by enhancing EGFR signaling. (PubMed, Genome Med)
    PRMT1-mediated H4R3me2a recruits SMARCA4, which promotes colorectal cancer progression by enhancing EGFR signaling.
    Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • PRMT1 (Protein Arginine Methyltransferase 1)
    over3years
    Positive outcome of first-line therapy for a SMARCA4-deficient thoracic sarcomatoid tumor. (PubMed, Int Cancer Conf J)
    Pembrolizumab plus carboplatin and pemetrexed resulted in significant response. This combination therapy showed potential for first-line systemic treatment of SMARCA4-deficient thoracic sarcomatoid tumors.
    Clinical • Journal • PD(L)-1 Biomarker
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    Keytruda (pembrolizumab) • carboplatin • pemetrexed
    almost4years
    Brg1 Inhibition Prevents Liver Fibrosis and Cholangiocarcinoma by Attenuating Progenitor Expansion. (PubMed, Hepatology)
    We have demonstrated the function of Brg1 in promoting HPC expansion, liver cirrhosis, and ultimately iCCA development in chronically injured livers, which is largely dependent on Wnt/β-catenin signaling. Our data suggest that therapies targeting Brg1-expressing HPCs are promising for the treatment of liver cirrhosis and iCCA.
    Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    4years
    Efficacy of Immune Checkpoint Inhibitors in SMARCA4-Mutant NSCLC. (PubMed, J Thorac Oncol)
    No abstract available
    Clinical • Journal • Checkpoint inhibition
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    SMARCA4 mutation
    over4years
    Brg1 regulates murine liver regeneration by targeting miR-187-5p dependent on Hippo signalling pathway. (PubMed, J Cell Mol Med)
    We identified LATS1 as a target gene of miR-187-5p and the introduction of miR-187-5p decrease the expression of LATS1 and inactivated the Hippo signalling pathway, which facilitated the expression of cell cycle-related proteins, and rescues the inhibitory effect of Brg1 in LR. Taken together, our findings suggested that deletion of Brg1 inhibits hepatocyte proliferation and LR by targeting miR-187-5p dependent on Hippo signalling pathway.
    Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)