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Ref Type Journal Article
PMID (26125128)
Authors Bitler BG, Fatkhutdinov N, Zhang R
Title Potential therapeutic targets in ARID1A-mutated cancers.
URL
Abstract Text ARID1A is a subunit of the Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex that regulates gene expression by controlling gene accessibility. ARID1A shows one of the highest mutation rates across different human cancer types. For example, ARID1A is mutated in ∼ 50% of ovarian clear cell carcinoma (OCCC). There is considerable interest in developing cancer therapeutics that correlate with ARID1A mutational status. A recent study demonstrated a synthetic lethality by targeting EZH2 histone methyltransferase activity in ARID1A-mutated OCCC using a clinically applicable small-molecule inhibitor. The observed synthetic lethality correlated with inhibition of PI3K/AKT signaling. In addition, there is evidence indicating that ARID1A-mutated cancer may also be subjected to therapeutic intervention by targeting residual SWI/SNF activity, the PI3K/AKT pathway, the DNA damage response, the tumor immunological microenvironment and stabilizing wild-type p53. In summary, we propose EZH2 inhibitor-based combinatorial strategies for targeting ARID1A-mutated cancers.

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Molecular Profile Treatment Approach
ARID1A Q758Rfs*75 EZH2 inhibitor
ARID1A Q802Vfs*32 EZH2 inhibitor
ARID1A G283fs EZH2 inhibitor
ARID1A R1276* EZH2 inhibitor
ARID1A K1603* EZH2 inhibitor
ARID1A Q1250* EZH2 inhibitor
ARID1A D1850Gfs*4 EZH2 inhibitor
ARID1A Q372* EZH2 inhibitor
ARID1A S1248* EZH2 inhibitor
ARID1A L2009_L2017del EZH2 inhibitor
ARID1A Q611Rfs*11 EZH2 inhibitor
ARID1A Y1431* EZH2 inhibitor
ARID1A Q1327Afs*11 EZH2 inhibitor
ARID1A N1192fs EZH2 inhibitor
ARID1A Q670* EZH2 inhibitor
ARID1A R1722* EZH2 inhibitor
ARID1A T1003fs EZH2 inhibitor
ARID1A S366Afs*25 EZH2 inhibitor
ARID1A M1224fs EZH2 inhibitor
ARID1A I908fs EZH2 inhibitor
ARID1A A1682fs EZH2 inhibitor
ARID1A A339Lfs*24 EZH2 inhibitor
ARID1A Q528* EZH2 inhibitor
ARID1A S584fs EZH2 inhibitor
ARID1A P726fs EZH2 inhibitor
ARID1A Q537* EZH2 inhibitor
ARID1A R727fs EZH2 inhibitor
ARID1A Q1342fs EZH2 inhibitor
ARID1A Q1403* EZH2 inhibitor
ARID1A Q515* EZH2 inhibitor
ARID1A P1326Rfs*155 EZH2 inhibitor
ARID1A Q920* EZH2 inhibitor
ARID1A T292fs EZH2 inhibitor
ARID1A A1559* EZH2 inhibitor
ARID1A G1450fs EZH2 inhibitor
ARID1A G108fs EZH2 inhibitor
ARID1A G276* EZH2 inhibitor
ARID1A Y395* EZH2 inhibitor
ARID1A G284fs EZH2 inhibitor
ARID1A W1545* EZH2 inhibitor
ARID1A Q1454* EZH2 inhibitor
ARID1A Q393fs EZH2 inhibitor
ARID1A Q1479* EZH2 inhibitor
ARID1A M923Hfs*13 EZH2 inhibitor
ARID1A Q1172* EZH2 inhibitor
ARID1A S769* EZH2 inhibitor
ARID1A E1780* EZH2 inhibitor
ARID1A S1184fs EZH2 inhibitor
ARID1A Q372Sfs*19 EZH2 inhibitor
ARID1A Q708* EZH2 inhibitor
ARID1A R750* EZH2 inhibitor
ARID1A T979fs EZH2 inhibitor
ARID1A G1351fs EZH2 inhibitor
ARID1A G1295fs EZH2 inhibitor
ARID1A S1153fs EZH2 inhibitor
ARID1A S958Lfs*10 EZH2 inhibitor
ARID1A Q449* EZH2 inhibitor
ARID1A Q1327fs EZH2 inhibitor
ARID1A Q288Pfs*112 EZH2 inhibitor
ARID1A Q474* EZH2 inhibitor
ARID1A A339Gfs*61 EZH2 inhibitor
ARID1A A345_A349del EZH2 inhibitor
ARID1A M1532fs EZH2 inhibitor
ARID1A S264* EZH2 inhibitor
ARID1A Q456* EZH2 inhibitor
ARID1A F1859fs EZH2 inhibitor
ARID1A F1823fs EZH2 inhibitor
ARID1A Q479* EZH2 inhibitor
ARID1A V1982fs EZH2 inhibitor
ARID1A P20_P21dup EZH2 inhibitor
ARID1A Q1519Pfs*13 EZH2 inhibitor
ARID1A R1721fs EZH2 inhibitor
ARID1A Y551Lfs*72 EZH2 inhibitor
ARID1A S1149* EZH2 inhibitor
ARID1A Q1519* EZH2 inhibitor
ARID1A M1154fs EZH2 inhibitor
ARID1A Q403* EZH2 inhibitor
ARID1A Q586* EZH2 inhibitor
ARID1A Q1346* EZH2 inhibitor
ARID1A W1073* EZH2 inhibitor
ARID1A S11fs EZH2 inhibitor
ARID1A Q1131* EZH2 inhibitor
ARID1A Q566* EZH2 inhibitor
ARID1A Q790* EZH2 inhibitor
ARID1A Y1324fs EZH2 inhibitor
ARID1A Q1584* EZH2 inhibitor
ARID1A E1836* EZH2 inhibitor
ARID1A S674fs EZH2 inhibitor
ARID1A Q546Rfs*73 EZH2 inhibitor
ARID1A H203fs EZH2 inhibitor
ARID1A S1623* EZH2 inhibitor
ARID1A Q766Pfs*51 EZH2 inhibitor
ARID1A Q543* EZH2 inhibitor
ARID1A S825fs EZH2 inhibitor
ARID1A W1973* EZH2 inhibitor
ARID1A P886Tfs*49 EZH2 inhibitor
ARID1A N917fs EZH2 inhibitor
ARID1A L1866fs EZH2 inhibitor
ARID1A Q1493* EZH2 inhibitor
ARID1A R774Efs*55 EZH2 inhibitor
ARID1A Q1200* EZH2 inhibitor
ARID1A E1776* EZH2 inhibitor
ARID1A Q1409* EZH2 inhibitor
ARID1A G277fs EZH2 inhibitor
ARID1A Q372Afs*28 EZH2 inhibitor
ARID1A Q1741* EZH2 inhibitor
ARID1A E1799fs EZH2 inhibitor
ARID1A Q1856* EZH2 inhibitor
ARID1A Q507fs EZH2 inhibitor
ARID1A Y518* EZH2 inhibitor
ARID1A P725fs EZH2 inhibitor
ARID1A S1791* EZH2 inhibitor
ARID1A Q1148* EZH2 inhibitor
ARID1A Q878* EZH2 inhibitor
ARID1A S705fs EZH2 inhibitor
ARID1A Q1334_R1335insQ EZH2 inhibitor
ARID1A R693* EZH2 inhibitor
ARID1A inact mut EZH2 inhibitor
ARID1A Q372fs EZH2 inhibitor
ARID1A G1711fs EZH2 inhibitor
ARID1A K1072Nfs*21 EZH2 inhibitor
ARID1A Q944* EZH2 inhibitor
ARID1A I1954fs EZH2 inhibitor
ARID1A P135Lfs*96 EZH2 inhibitor
ARID1A Q1397fs EZH2 inhibitor
ARID1A S261* EZH2 inhibitor
ARID1A Y788* EZH2 inhibitor
ARID1A Q1401* EZH2 inhibitor
ARID1A E1777* EZH2 inhibitor
ARID1A T294Pfs*69 EZH2 inhibitor
ARID1A Q581* EZH2 inhibitor
ARID1A M1215fs EZH2 inhibitor
ARID1A W1670* EZH2 inhibitor
ARID1A P224fs EZH2 inhibitor
ARID1A L714fs EZH2 inhibitor
ARID1A T897Lfs*22 EZH2 inhibitor
ARID1A Q585* EZH2 inhibitor
ARID1A L657Pfs*81 EZH2 inhibitor
ARID1A S621fs EZH2 inhibitor
ARID1A E992* EZH2 inhibitor
ARID1A G2087R EZH2 inhibitor
ARID1A D1838* EZH2 inhibitor
ARID1A D1850fs EZH2 inhibitor
ARID1A Q480* EZH2 inhibitor
ARID1A A1522Pfs*5 EZH2 inhibitor
ARID1A A1978Sfs*36 EZH2 inhibitor
ARID1A G276Efs*87 EZH2 inhibitor
ARID1A Q502* EZH2 inhibitor
ARID1A Q1212* EZH2 inhibitor
ARID1A Q548fs EZH2 inhibitor
ARID1A E1006* EZH2 inhibitor
ARID1A G671Efs*71 EZH2 inhibitor
ARID1A R1989* EZH2 inhibitor
ARID1A P1867fs EZH2 inhibitor
ARID1A Q1095* EZH2 inhibitor
ARID1A F1118fs EZH2 inhibitor
ARID1A K1071fs EZH2 inhibitor
ARID1A R1446* EZH2 inhibitor
ARID1A Y1285fs EZH2 inhibitor
ARID1A D1850Tfs*33 EZH2 inhibitor
ARID1A S711* EZH2 inhibitor
ARID1A E1733* EZH2 inhibitor
ARID1A Q1835* EZH2 inhibitor
ARID1A Y551Tfs*68 EZH2 inhibitor
ARID1A E654Gfs*9 EZH2 inhibitor
ARID1A E1718* EZH2 inhibitor
ARID1A P94Lfs*7 EZH2 inhibitor
ARID1A R1335* EZH2 inhibitor
ARID1A Q1894* EZH2 inhibitor
ARID1A Y2254* EZH2 inhibitor
ARID1A Q199* EZH2 inhibitor
ARID1A Y823fs EZH2 inhibitor
ARID1A S617* EZH2 inhibitor
ARID1A Q1142* EZH2 inhibitor
ARID1A V1561fs EZH2 inhibitor
ARID1A S138* EZH2 inhibitor
ARID1A G83Wfs*28 EZH2 inhibitor
ARID1A L1092* EZH2 inhibitor
ARID1A Q1519Rfs*8 EZH2 inhibitor
ARID1A Q1512* EZH2 inhibitor
ARID1A G925* EZH2 inhibitor
ARID1A S664* EZH2 inhibitor
ARID1A G319fs EZH2 inhibitor
ARID1A P224Rfs*8 EZH2 inhibitor
ARID1A G1848fs EZH2 inhibitor
ARID1A Q393* EZH2 inhibitor
ARID1A Q920fs EZH2 inhibitor
ARID1A E1964* EZH2 inhibitor
ARID1A Q1519fs EZH2 inhibitor
ARID1A R1461* EZH2 inhibitor
ARID1A P1898Hfs*25 EZH2 inhibitor
ARID1A E1764* EZH2 inhibitor
ARID1A E1596* EZH2 inhibitor
ARID1A Q268* EZH2 inhibitor
ARID1A A35Gfs*76 EZH2 inhibitor
ARID1A R1721* EZH2 inhibitor
ARID1A E896* EZH2 inhibitor
ARID1A G272fs EZH2 inhibitor
ARID1A loss EZH2 inhibitor
ARID1A Y592* EZH2 inhibitor
ARID1A Q1631* EZH2 inhibitor
ARID1A Q611* EZH2 inhibitor
ARID1A del EZH2 inhibitor
ARID1A negative EZH2 inhibitor
ARID1A M1318fs EZH2 inhibitor
ARID1A Q405* EZH2 inhibitor
ARID1A R1528* EZH2 inhibitor
ARID1A Q633* EZH2 inhibitor
ARID1A Q199fs EZH2 inhibitor
ARID1A S1868fs EZH2 inhibitor
ARID1A G1847fs EZH2 inhibitor
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References