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| Profile Name | ARID1A A35Gfs*76 |
| Gene Variant Detail | |
| Relevant Treatment Approaches | EZH2 inhibitor |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| ARID1A mutant | ovarian cancer | sensitive | GSK126 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, GSK126 selectively inhibited growth of ARID1A-mutant ovarian cancer cells in culture, and induced tumor regression in ARID1A-mutant ovarian cancer xenograft models (PMID: 25686104). | 25686104 |
| ARID1A mutant | ovarian cancer | sensitive | UNC1999 | Preclinical - Cell culture | Actionable | In a preclinical study, UNC1999 inhibited growth of ovarian cancer cell lines harboring ARID1A mutations in culture (PMID: 25686104). | 25686104 |
| ARID1A mutant | ovarian clear cell carcinoma | sensitive | Dasatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Sprycel (dasatinib) resulted in decreased cell growth of ovarian clear cell carcinoma (OCCC) cells harboring an ARID1A mutation in culture and anti-tumor activity in cell line xenograft models of OCCC (PMID: 27364904). | 27364904 |
| ARID1A mutant | renal cell carcinoma | predicted - sensitive | Bevacizumab + Everolimus | Case Reports/Case Series | Actionable | In a Phase II trial, 100% (7/7) of patients with papillary renal cell carcinoma (n=3) or unclassified renal cell carcinoma with papillary features (n=4) harboring ARID1A mutations achieved the primary endpoint of 6-month progression-free survival when treated with the combination of Afinitor (everolimus) and Avastin (bevacizumab) (PMID: 32975815; NCT01399918). | 32975815 |
| ARID1A mutant | ovarian clear cell carcinoma | sensitive | VE-821 | Preclinical - Cell culture | Actionable | In a preclinical study, ovarian clear cell carcinoma cells harboring an ARID1A mutation were sensitive to VE-821 in in vitro assays, demonstrating decreased cell survival (PMID: 27958275). | 27958275 |
| ARID1A mutant | ovarian clear cell carcinoma | sensitive | Berzosertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Berzosertib (VX-970) treatment in ovarian clear cell carcinoma cells harboring an ARID1A mutation resulted in decreased cell survival and induction of DNA damage and apoptosis in culture, and tumor growth inhibition in cell line xenograft models (PMID: 27958275). | 27958275 |
| ARID1A mutant | Advanced Solid Tumor | predicted - sensitive | unspecified PD-1 antibody | Clinical Study - Cohort | Actionable | In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in significantly longer median progression-free survival (PFS, 11 vs 4 months, p=0.006) in patients with ARID1A-altered (n=46) tumors than in patients with ARID1A wild-type (n=329) tumors, and improved overall survival (31 vs 20 months, p=0.13), ARID1A alterations predicted longer PFS (HR=0.61, p=0.02) after immune checkpoint inhibitor therapies independent of MSI or TMB status (PMID: 32111729). | 32111729 |
| ARID1A mutant | Advanced Solid Tumor | predicted - sensitive | unspecified PD-L1 antibody | Clinical Study - Cohort | Actionable | In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in significantly longer median progression-free survival (PFS, 11 vs 4 months, p=0.006) in patients with ARID1A-altered (n=46) tumors than in patients with ARID1A wild-type (n=329) tumors, and improved overall survival (31 vs 20 months, p=0.13), ARID1A alterations predicted longer PFS (HR=0.61, p=0.02) after immune checkpoint inhibitor therapies independent of MSI or TMB status (PMID: 32111729). | 32111729 |
| ARID1A mutant | endometrial cancer | predicted - sensitive | unspecified PD-L1 antibody | Clinical Study - Cohort | Actionable | In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in significantly longer median progression-free survival (4.6 vs 3.0 months, p=0.02) in patients with ARID1A-altered (n=10) endometrial cancer than in patients with ARID1A wild-type (n=13) tumors (PMID: 32111729). | 32111729 |
| ARID1A mutant | endometrial cancer | predicted - sensitive | unspecified PD-1 antibody | Clinical Study - Cohort | Actionable | In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in significantly longer median progression-free survival (4.6 vs 3.0 months, p=0.02) in patients with ARID1A-altered (n=10) endometrial cancer than in patients with ARID1A wild-type (n=13) tumors (PMID: 32111729). | 32111729 |
| ARID1A mutant | gastroesophageal cancer | predicted - sensitive | unspecified PD-1 antibody | Clinical Study - Cohort | Actionable | In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in longer median progression-free survival (11.4 vs 2.5 months, p=0.21) in patients with ARID1A-altered (n=5) gastroesophageal cancer than in patients with ARID1A wild-type (n=16) tumors (PMID: 32111729). | 32111729 |
| ARID1A mutant | gastroesophageal cancer | predicted - sensitive | unspecified PD-L1 antibody | Clinical Study - Cohort | Actionable | In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in longer median progression-free survival (11.4 vs 2.5 months, p=0.21) in patients with ARID1A-altered (n=5) gastroesophageal cancer than in patients with ARID1A wild-type (n=16) tumors (PMID: 32111729). | 32111729 |
| ARID1A mutant | colorectal cancer | predicted - sensitive | unspecified PD-L1 antibody | Clinical Study - Cohort | Actionable | In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in significantly longer median progression-free survival (5.2 vs 2.1 months, p=0.005) in patients with ARID1A-altered (n=12) colorectal cancer than in patients with ARID1A wild-type (n=37) tumors (PMID: 32111729). | 32111729 |
| ARID1A mutant | colorectal cancer | predicted - sensitive | unspecified PD-1 antibody | Clinical Study - Cohort | Actionable | In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in significantly longer median progression-free survival (5.2 vs 2.1 months, p=0.005) in patients with ARID1A-altered (n=12) colorectal cancer than in patients with ARID1A wild-type (n=37) tumors (PMID: 32111729). | 32111729 |
| ARID1A mutant | melanoma | predicted - sensitive | unspecified PD-1 antibody | Clinical Study - Cohort | Actionable | In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in longer median progression-free survival (45.4 vs 3.0 months, p=0.08) in patients with ARID1A-altered (n=6) melanoma than in patients with ARID1A wild-type (n=91) tumors (PMID: 32111729). | 32111729 |
| ARID1A mutant | melanoma | predicted - sensitive | unspecified PD-L1 antibody | Clinical Study - Cohort | Actionable | In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in longer median progression-free survival (45.4 vs 3.0 months, p=0.08) in patients with ARID1A-altered (n=6) melanoma than in patients with ARID1A wild-type (n=91) tumors (PMID: 32111729). | 32111729 |
| ARID1A mutant | lung non-small cell carcinoma | predicted - sensitive | unspecified PD-L1 antibody | Clinical Study - Cohort | Actionable | In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in longer but not statistically significant median progression-free survival (8.7 vs 4.6 months, p=0.53) in patients with ARID1A-altered (n=7) non-small cell lung cancer than in patients with ARID1A wild-type (n=104) tumors (PMID: 32111729). | 32111729 |
| ARID1A mutant | lung non-small cell carcinoma | predicted - sensitive | unspecified PD-1 antibody | Clinical Study - Cohort | Actionable | In a retrospective analysis, anti-PD-1/PD-L1 therapies resulted in longer but not statistically significant median progression-free survival (8.7 vs 4.6 months, p=0.53) in patients with ARID1A-altered (n=7) non-small cell lung cancer than in patients with ARID1A wild-type (n=104) tumors (PMID: 32111729). | 32111729 |
| ARID1A mutant | bladder urothelial carcinoma | predicted - sensitive | Nivolumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, metastatic urothelial carcinoma patients from the CheckMate275 trial harboring an ARID1A mutation (n=39) demonstrated a greater overall survival (11.4 mo vs 6.0 mo; P=0.03) compared to patients with wild-type ARID1A (n=100) when treated with Opdivo (nivolumab) (PMID: 32554706; NCT02387996). | 32554706 |
| ARID1A mutant | bladder urothelial carcinoma | predicted - sensitive | Atezolizumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, metastatic urothelial carcinoma patients from the IMvigor210 trial harboring an ARID1A mutation (n=62) demonstrated a greater overall survival (15.4 mo vs 8.2 mo; P=0.03) compared to patients with wild-type ARID1A (n=213) when treated with Tecentriq (atezolizumab) (PMID: 32554706; NCT02108652). | 32554706 |
| ARID1A 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 ARID1A, 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 |
| ARID1A 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 ARID1A, 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 |
| ARID1A 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 ARID1A, 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 |
| ARID1A 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 ARID1A, 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 |
| ARID1A 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 ARID1A, 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 |
| ARID1A inact mut | renal cell carcinoma | 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 ARID1A, correlated with improved survival in one cohort of patients with renal cell carcinoma treated with systemic immune checkpoint inhibitors but not the other, with adjusted HRs for overall survival of 0.33 (p=0.004, n=68) and 1.04 (p=0.906, n=118), respectively (PMID: 32321774). | 32321774 |
| ARID1A inact mut | lung non-small cell carcinoma | 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 ARID1A, correlated with worse survival in one cohort of patients with non-small cell lung cancer treated with systemic immune checkpoint inhibitors but not the other, with adjusted HRs for overall survival of 1.44 (p=0.018, n=334) and 1.84 (p=0.379, n=255), respectively (PMID: 32321774). | 32321774 |
| ARID1A inact mut | urinary bladder cancer | sensitive | GSK126 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, GSK126 inhibited cell viability in bladder cancer cell lines harboring ARID1A inactivating mutations in culture and inhibited tumor growth in patient-derived xenograft (PDX) and cell line xenograft models of bladder cancer harboring ARID1A inactivating mutations (PMID: 35852858). | 35852858 |
| ARID1A inact mut | urinary bladder cancer | sensitive | CPI-1205 | Preclinical - Cell culture | Actionable | In a preclinical study, CPI-1205 inhibited viability of bladder cancer cell lines harboring ARID1A inactivating mutations in culture (PMID: 35852858). | 35852858 |
| ARID1A inact mut | urinary bladder cancer | sensitive | Tazemetostat | Preclinical - Cell culture | Actionable | In a preclinical study, Tazverik (tazemetostat) inhibited viability of bladder cancer cell lines harboring ARID1A inactivating mutations in culture (PMID: 35852858). | 35852858 |
| ARID1A inact mut | urinary bladder cancer | sensitive | MAK683 | Preclinical - Cell culture | Actionable | In a preclinical study, MAK683 inhibited viability of bladder cancer cell lines harboring ARID1A inactivating mutations in culture (PMID: 35852858). | 35852858 |
| ARID1A inact mut | urinary bladder cancer | sensitive | Pictilisib | Preclinical - Cell culture | Actionable | In a preclinical study, Pictilisib (GDC-0941) inhibited viability of bladder cancer cell lines harboring ARID1A inactivating mutations in culture (PMID: 35852858). | 35852858 |
| ARID1A inact mut | female reproductive organ cancer | no benefit | PLX2853 | Phase II | Actionable | In a Phase IIa trial, PLX2853 treatment demonstrated safety but failed to meet predetermined criteria for efficacy in patients with advanced gynecologic cancers harboring a pathogenic ARID1A mutation, resulting in a partial response in 7.1% (1/14, 1 patient with endometrial carcinoma) and stable disease in 35.7% (5/14) of evaluable patients (PMID: 37797273; NCT04493619). | 37797273 |
| ARID1A mutant | stomach cancer | predicted - sensitive | M1774 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, M1774 inhibited tumor growth in a cell line xenograft model of gastric cancer harboring an ARID1A mutation (PMID: 38407317). | 38407317 |
| ARID1A inact mut | urinary bladder cancer | sensitive | Tulmimetostat | Preclinical - Pdx | Actionable | In a preclinical study, Tulmimetostat inhibited tumor growth in a bladder cancer patient-derived xenograft (PDX) model harboring a loss of function mutation in ARID1A (PMID: 38833522). | 38833522 |
| ARID1A inact mut | endometrial cancer | sensitive | Tulmimetostat | Preclinical - Pdx | Actionable | In a preclinical study, Tulmimetostat inhibited tumor growth in endometrial cancer patient-derived xenograft (PDX) models harboring loss of function mutations in ARID1A (PMID: 38833522). | 38833522 |
| ARID1A inact mut | ovarian cancer | predicted - sensitive | HM97662 | Preclinical | Actionable | In a preclinical study, HM97662 treatment inhibited tumor growth in a xenograft model of ovarian cancer harboring an ARID1A loss-of-function mutation (Cancer Res (2024) 84 (6_Supplement): 3240). | detail... |
| ARID1A inact mut | urinary bladder cancer | predicted - sensitive | HM97662 | Preclinical | Actionable | In a preclinical study, HM97662 treatment inhibited tumor growth in a xenograft model of bladder cancer harboring an ARID1A loss-of-function mutation (Cancer Res (2024) 84 (6_Supplement): 3240). | detail... |
| ARID1A inact mut | lung small cell carcinoma | predicted - sensitive | HM97662 | Preclinical | Actionable | In a preclinical study, HM97662 treatment inhibited tumor growth in a xenograft model of small cell lung cancer harboring an ARID1A mutation (Cancer Res (2024) 84 (6_Supplement): 3240). | detail... |
| ARID1A inact mut | prostate cancer | predicted - sensitive | HM97662 | Preclinical | Actionable | In a preclinical study, HM97662 treatment inhibited tumor growth in a xenograft model of prostate cancer harboring an ARID1A mutation (Cancer Res (2024) 84 (6_Supplement): 3240). | detail... |
| ARID1A inact mut | stomach cancer | predicted - sensitive | HM97662 | Preclinical | Actionable | In a preclinical study, HM97662 treatment inhibited tumor growth in a xenograft model of gastric cancer harboring an ARID1A mutation (Cancer Res (2024) 84 (6_Supplement): 3240). | detail... |