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Gene | SMARCA4 |
Variant | inact mut |
Impact List | unknown |
Protein Effect | loss of function |
Gene Variant Descriptions | SMARCA4 inact mut indicates that this variant results in a loss of function of the Smarca4 protein. However, the specific amino acid change has not been identified. |
Associated Drug Resistance | |
Category Variants Paths |
SMARCA4 mutant SMARCA4 inact mut |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
SMARCA4 inact mut | lung non-small cell carcinoma | sensitive | Alisertib | Preclinical - Cell culture | Actionable | In a preclinical study, a non-small cell lung cancer cell line harboring an inactivating mutation in SMARCA4 demonstrated sensitivity to Alisertib (MLN8237) in culture (PMID: 28102363). | 28102363 |
SMARCA4 inact mut | lung non-small cell carcinoma | sensitive | Danusertib | Preclinical - Cell culture | Actionable | In a preclinical study, a non-small cell lung cancer cell line harboring an inactivating mutation in SMARCA4 demonstrated sensitivity to Danusertib (PHA-739358) in culture (PMID: 28102363). | 28102363 |
SMARCA4 inact mut | lung non-small cell carcinoma | sensitive | ENMD-2076 | Preclinical - Cell culture | Actionable | In a preclinical study, a non-small cell lung cancer cell line harboring an inactivating mutation in SMARCA4 demonstrated sensitivity to ENMD-2076 in culture (PMID: 28102363). | 28102363 |
SMARCA4 inact mut | Advanced Solid Tumor | no benefit | Palbociclib | Clinical Study | Actionable | In a combined analysis of 2 clinical trials (DRUP, MoST), Ibrance (palbociclib) or Kisqali (ribociclib) monotherapy had limited efficacy and resulted in no objective responses, a 15% clinical benefit rate at 16 weeks, median progression-free survival of 4 mo, and median overall survival of 5 mo in previously treated advanced solid tumor patients (n=112) with inactivating SMARCA4 mutations, CDKN2A loss, or CDK4, CDK6, CCND1, CCND2, or CCND3 amplification (PMID: 37424386; NCT02925234, ACTRN12616000931471). | 37424386 |
SMARCA4 inact mut | lung non-small cell carcinoma | sensitive | Tozasertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, non-small cell lung cancer cell lines harboring SMARCA4 inactivating mutations demonstrated sensitivity to Tozasertib (VX-680) in culture and in xenograft models (PMID: 28102363). | 28102363 |
SMARCA4 inact mut | lung non-small cell carcinoma | sensitive | MK-5108 | Preclinical - Cell culture | Actionable | In a preclinical study, a non-small cell lung cancer cell line harboring an inactivating mutation in SMARCA4 demonstrated sensitivity to MK-5108 (VX-689) in culture (PMID: 28102363). | 28102363 |
SMARCA4 inact mut | melanoma | not predictive | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including SMARCA4, did not correlate with improved survival in 2 separate cohorts of patients with melanoma treated with systemic immune checkpoint inhibitors, with adjusted HRs for overall survival of 1.70 (p=0.192, n=86) and 1.02 (p=0.939, n=192), respectively (PMID: 32321774). | 32321774 |
SMARCA4 inact mut | transitional cell carcinoma | not predictive | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including SMARCA4, did not correlate with improved survival in 2 separate cohorts of patients with transitional cell carcinoma treated with systemic immune checkpoint inhibitors, with adjusted HRs for overall survival of 1.44 (p=0.34, n=56) and 0.82 (p=0.559, n=93), respectively (PMID: 32321774). | 32321774 |
SMARCA4 inact mut | head and neck squamous cell carcinoma | not predictive | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including SMARCA4, did not correlate with improved survival in 2 separate cohorts of patients with head and neck squamous cell carcinoma treated with systemic immune checkpoint inhibitors, with adjusted HRs for overall survival of 0.74 (p=0.631, n=31) and 0.76 (p=0.622, n=68), respectively (PMID: 32321774). | 32321774 |
SMARCA4 inact mut | colorectal adenocarcinoma | unknown | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including SMARCA4, correlated with improved survival in one cohort of patients with colorectal adenocarcinoma treated with systemic immune checkpoint inhibitors but not the other, with adjusted HRs for overall survival of 0.30 (p=0.03, n=35) and 0.56 (p=0.244, n=63), respectively (PMID: 32321774). | 32321774 |
SMARCA4 inact mut | gastroesophageal adenocarcinoma | not predictive | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including SMARCA4, did not correlate with improved survival in 2 separate cohorts of patients with gastroesophageal adenocarcinoma treated with systemic immune checkpoint inhibitors, with adjusted HRs for overall survival of 0.70 (p=0.403, n=66) and 0.46 (p=0.071, n=59), respectively (PMID: 32321774). | 32321774 |