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Profile Name ARID1A S2269L
Gene Variant Detail

ARID1A S2269L (unknown)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
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-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 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 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 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 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-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 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 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 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 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 renal cell carcinoma predicted - sensitive Bevacizumab + Everolimus Phase II Actionable In a Phase II trial, 100% (5/5) of renal cell carcinoma patients harboring ARID1A mutations achieved the primary endpoint of 6 month PFS when treated with the combination therapy Afinitor (everolimus) and Avastin (bevacizumab) (PMID: 27601542). 27601542
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 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 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 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 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 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 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 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 mut PIK3CA act mut ovarian cancer sensitive GSK126 Preclinical - Cell culture Actionable In a preclinical study, expression of a constitutively active PIK3CA mutation in ARID1A-mutant ovarian cancer cell lines enhanced growth inhibition by GSK126 in culture (PMID: 25686104). 25686104
ARID1A loss ovarian clear cell carcinoma predicted - sensitive JQ1 Preclinical - Cell culture Actionable In a preclinical study, knockout of ARID1A in ovarian clear cell carcinoma cell lines resulted in increased sensitivity to growth inhibition by JQ1 compared to cells with wild-type ARID1A in culture (PMID: 29760405). 29760405
ARID1A loss Her2-receptor positive breast cancer resistant AZD8055 Preclinical - Cell culture Actionable In a preclinical study, ERBB2 (HER2) positive breast cancer cells with ARID1A loss demonstrated resistance to AZD8055 in culture (PMID: 27172896). 27172896
ARID1A loss ovarian cancer predicted - sensitive unspecified PD-L1 antibody Preclinical Actionable In a preclinical study, an ARID1A-deficient orthotopic ovarian cancer mouse model treated with a PD-L1 antibody demonstrated improved survival and greater decreased tumor volume compared to those treated with control (PMID: 29736026). 29736026
ARID1A loss colon cancer predicted - sensitive unspecified PD-L1 antibody Preclinical - Cell line xenograft Actionable In a preclinical study, ARID1A-deficient colon cancer xenograft models demonstrated an increased response to treatment with an anti-PD-L1 antibody compared to controls (PMID: 29736026). 29736026
ARID1A loss breast cancer sensitive AZD8055 + MK2206 Preclinical - Cell culture Actionable In a preclinical study, breast cancer cells with loss of ARID1A demonstrated restored sensitivity to AZD8055 when additionally treated with MK2206 in culture (PMID: 27172896). 27172896
ARID1A loss Her2-receptor positive breast cancer resistant Trastuzumab Preclinical - Cell culture Actionable In a preclinical study, ERBB2 (HER2) positive breast cancer cells with ARID1A loss demonstrated resistance to Herceptin (trastuzumab) in culture (PMID: 27172896). 27172896
ARID1A loss ERBB2 amp breast cancer sensitive MK2206 + Trastuzumab Preclinical - Cell culture Actionable In a preclinical study, a breast cancer cell line with ARID1A loss and harboring ERBB2 (HER2) amplification demonstrated restored sensitivity to Herceptin (trastuzumab) when additionally treated with MK2206 in culture (PMID: 27172896). 27172896
ARID1A negative ovarian clear cell carcinoma predicted - sensitive ENMD-2076 Phase II Actionable In a Phase II trial, ENMD-2076 treatment resulted a median progression-free survival (PFS) of 4.4 months in patients with ARIDA1A-negative recurrent ovarian clear cell carcinoma and a median PFS of 3.6 months in ARID1A-positive patients, with a statistically significant difference in estimated 6-month PFS rate (0.33 vs 0.12, p=0.023) (PMID: 30108107). 30108107
ARID1A Q1148* ovarian clear cell carcinoma predicted - sensitive JQ1 Preclinical - Pdx Actionable In a preclinical study, JQ1 inhibited tumor growth in an ovarian clear cell carcinoma patient-derived xenograft (PDX) model harboring ARID1A Q1148*, but did not inhibit growth in a model with wild-type ARID1A (PMID: 29760405). 29760405
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 prostate cancer predicted - sensitive Olaparib Case Reports/Case Series Actionable In a Phase II (TOPARP-B) trial, Lynparza (olaparib) treatment resulted in a composite overall response rate of 20.0% (4/20) and a RECIST objective response rate of 0% (0/17) in patients with castration-resistant prostate cancer harboring deleterious mutations in DNA damage response genes, including ARID1A, ATRX, CHEK1/2, FANCA, FANCF, FANCG, FANCI, FANCM, MSH2, NBN, RAD50, and WRN (n=1, 1, 1, 5, 5, 2, 1, 1, 2, 1, 1, 1, 7, respectively) (PMID: 31806540; NCT01682772). 31806540
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 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 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 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 dec exp ovarian cancer sensitive Talazoparib Preclinical - Cell culture Actionable In a preclinical study, knockdown of ARID1A resulted in increased sensitivity to Talazoparib (BMN-673) in ovarian cancer cells in culture (PMID: 26069190). 26069190
ARID1A dec exp breast cancer sensitive Olaparib Preclinical Actionable In a preclinical study, Lynparza (olaparib) inhibited colony formation of human mammary epithelial cells and inhibited proliferation of a human breast cancer cell line after knockdown of ARID1A in culture (PMID: 26069190). 26069190
ARID1A dec exp breast cancer sensitive Rucaparib Preclinical - Cell culture Actionable In a preclinical study, Rubraca (rucaparib) inhibited colony formation of human mammary epithelial cells and inhibited proliferation of a human breast cancer cell line after knockdown of ARID1A in culture (PMID: 26069190). 26069190
ARID1A dec exp breast cancer conflicting Talazoparib Preclinical - Cell line xenograft Actionable In a preclinical study, Talazoparib (BMN-673) selectively inhibited growth and induced apoptosis in breast cancer cells with knock-down of ARID1A in culture, and inhibited tumor growth in ARID1A-deficient breast cancer cell line xenograft models (PMID: 26069190). 26069190
ARID1A dec exp breast cancer conflicting Talazoparib Preclinical - Cell culture Actionable In a preclinical study, human mammary epithelial cells with knockdown of ARID1A demonstrated resistance to Talazoparib (BMN673) when compared to parental cells in culture (PMID: 29669295). 29669295
ARID1A dec exp ovarian cancer predicted - sensitive APR-246 Preclinical - Cell line xenograft Actionable In a preclinical study, ovarian cancer cells with ARID1A-deficiency via knockdown were sensitive to treatment with APR-246, demonstrating decreased cell survival and reduced colony formation in culture and tumor growth suppression in cell-line xenograft models (PMID: 30686770). 30686770
ARID1A dec exp ovarian cancer sensitive GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 inhibited growth of ovarian cancer cells with knockdown of ARID1A expression in culture (PMID: 25686104). 25686104
ARID1A dec exp ovarian cancer predicted - sensitive Buthionine sulfoximine Preclinical - Cell line xenograft Actionable In a preclinical study, ovarian cancer cells with ARID1A-deficiency via knockdown were sensitive to treatment with Buthionine sulfoximine (BSO), demonstrating decreased cell survival and reduced colony formation in culture and tumor growth suppression in cell-line xenograft models (PMID: 30686770). 30686770
ARID1A dec exp ovarian clear cell carcinoma predicted - sensitive Molibresib Preclinical - Cell culture Actionable In a preclinical study, knockdown of ARID1A resulted in increased sensitivity to Molibresib (GSK525762) in ovarian clear cell carcinoma cell lines in culture (PMID: 29760405). 29760405
ARID1A dec exp breast cancer sensitive Veliparib Preclinical - Cell culture Actionable In a preclinical study, Veliparib (ABT-888) inhibited colony formation of human mammary epithelial cells and inhibited proliferation of a human breast cancer cell line after knockdown of ARID1A in culture (PMID: 26069190). 26069190
AKT1 pos ARID1A dec exp stomach cancer sensitive Fluorouracil + GSK690693 Preclinical - Cell culture Actionable In a preclinical study, GSK690693 in combination with Adrucil (fluorouracil) resulted in enhanced reduction in cell viability and induced apoptosis in in ARID1A knockdown gastric cancer cell lines expressing AKT1 in culture (PMID: 28860825). 28860825
AKT1 pos ARID1A dec exp stomach cancer sensitive GSK690693 Preclinical - Cell culture Actionable In a preclinical study, GSK690693 treatment inhibited phosphorylation of Akt and S6, reduced viability and induced apoptosis in ARID1A knockdown gastric cancer cell lines expressing AKT1 in culture (PMID: 28860825). 28860825
AKT1 pos ARID1A dec exp stomach cancer sensitive Cisplatin + GSK690693 Preclinical - Cell culture Actionable In a preclinical study, GSK690693 in combination with Platinol (cisplatin) resulted in enhanced reduction in cell viability and induced apoptosis in ARID1A knockdown gastric cancer cell lines expressing AKT1 in culture (PMID: 28860825). 28860825
ARID1A Q456* colorectal cancer sensitive Talazoparib Preclinical - Cell line xenograft Actionable In a preclinical study, Talazoparib (BMN-673) inhibited colony formation and proliferation of a human colorectal cancer cell line harboring ARID1A Q456* in culture and inhibited tumor formation in colorectal cancer xenografts harboring ARID1A Q456* (PMID: 26069190). 26069190
ARID1A Q456* colorectal cancer sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, a colorectal cancer cell line homozygously expressing ARID1A Q456* demonstrated sensitivity to treatment with Sprycel (dasatinib) in culture (PMID: 27364904). 27364904
ARID1A Q456* colorectal cancer sensitive Rucaparib Preclinical - Cell culture Actionable In a preclinical study, Rubraca (rucaparib) treatment resulted in increased apoptosis of colorectal cancer cells harboring ARID1A Q456* in culture (PMID: 26069190). 26069190
ARID1A Q456* colorectal cancer sensitive VE-821 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells homozygous for ARID1A Q456* were sensitive to VE-821 in in vitro assays, demonstrating decrease cell survival (PMID: 27958275). 27958275
ARID1A Q456* colorectal cancer sensitive Berzosertib Preclinical - Cell line xenograft Actionable In a preclinical study, Berzosertib (VX-970) treatment in colorectal cancer cells homozygous for ARID1A Q456* resulted in decreased cell survival in culture, and tumor growth inhibition in cell line xenograft models (PMID: 27958275). 27958275
ARID1A Q456* colorectal cancer sensitive Olaparib Preclinical Actionable In a preclinical study, Lynparza (olaparib) inhibited proliferation and colony formation of a colorectal cancer cell line harboring ARID1A Q456* in culture (PMID: 26069190). 26069190
ARID1A wild-type ovarian cancer no benefit GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 had no significant effect on the growth of ovarian cancer cells with wild-type ARID1A in culture (PMID: 25686104). 25686104
Clinical Trial Phase Therapies Title Recruitment Status