Combined inhibition of PI3K and Src kinases demonstrates synergistic therapeutic efficacy in clear-cell renal carcinoma

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Combined inhibition of PI3K and Src kinases demonstrates synergistic therapeutic efficacy in clear-cell renal carcinoma

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This article has been corrected. Correction in: Oncotarget. 2019; 10:2236.https://www.oncotarget.com/article/26807/. International audience. Potent inhibitors of PI3K (GDC-0941) and Src (Saracatinib) exhibit as individualagents, excellent oral anticancer activity in preclinical models and have enteredphase II clinical trials in various cancers. We found that PI3K and Src kinases aredysregulated in clear cell renal carcinomas (ccRCCs), an aggressive disease withouteffective targeted therapies. In this study we addressed this challenge by testingGDC-0941 and Saracatinib as either single agents or in combination in ccRCC celllines, as well as in mouse and PDX models. Our findings demonstrate that combinedinhibition of PI3K and Src impedes cell growth and invasion and induces cell deathof renal carcinoma cells providing preclinical evidence for a pairwise combinationof these anticancer drugs as a rational strategy to improve renal cancer treatment

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