PT - JOURNAL ARTICLE AU - Miller, Rowan E. AU - Brough, Rachel AU - Bajrami, Ilirjana AU - Williamson, Chris T. AU - McDade, Simon AU - Campbell, James AU - Kigozi, Asha AU - Rafiq, Rumana AU - Pemberton, Helen AU - Natrajan, Rachel AU - Joel, Josephine AU - Astley, Holly AU - Mahoney, Claire AU - Moore, Jonathan D. AU - Torrance, Chris AU - Gordan, John D. AU - Webber, James T. AU - Levin, Rebecca S. AU - Shokat, Kevan M. AU - Bandyopadhyay, Sourav AU - Lord, Christopher J. AU - Ashworth, Alan TI - Synthetic Lethal Targeting of <em>ARID1A</em>-Mutant Ovarian Clear Cell Tumors with Dasatinib AID - 10.1158/1535-7163.MCT-15-0554 DP - 2016 Jul 01 TA - Molecular Cancer Therapeutics PG - 1472--1484 VI - 15 IP - 7 4099 - http://mct.aacrjournals.org/content/15/7/1472.short 4100 - http://mct.aacrjournals.org/content/15/7/1472.full SO - Mol Cancer Ther2016 Jul 01; 15 AB - New targeted approaches to ovarian clear cell carcinomas (OCCC) are needed, given the limited treatment options in this disease and the poor response to standard chemotherapy. Using a series of high-throughput cell-based drug screens in OCCC tumor cell models, we have identified a synthetic lethal (SL) interaction between the kinase inhibitor dasatinib and a key driver in OCCC, ARID1A mutation. Imposing ARID1A deficiency upon a variety of human or mouse cells induced dasatinib sensitivity, both in vitro and in vivo, suggesting that this is a robust synthetic lethal interaction. The sensitivity of ARID1A-deficient cells to dasatinib was associated with G1–S cell-cycle arrest and was dependent upon both p21 and Rb. Using focused siRNA screens and kinase profiling, we showed that ARID1A-mutant OCCC tumor cells are addicted to the dasatinib target YES1. This suggests that dasatinib merits investigation for the treatment of patients with ARID1A-mutant OCCC. Mol Cancer Ther; 15(7); 1472–84. ©2016 AACR.