Combined inhibition of PI3K and Src kinases demonstrates synergistic therapeutic efficacy in clear-cell renal carcinoma
Résumé
Potent inhibitors of PI3K (GDC-0941) and Src (Saracatinib) exhibit as individual
agents, excellent oral anticancer activity in preclinical models and have entered
phase II clinical trials in various cancers. We found that PI3K and Src kinases are
dysregulated in clear cell renal carcinomas (ccRCCs), an aggressive disease without
effective targeted therapies. In this study we addressed this challenge by testing
GDC-0941 and Saracatinib as either single agents or in combination in ccRCC cell
lines, as well as in mouse and PDX models. Our findings demonstrate that combined
inhibition of PI3K and Src impedes cell growth and invasion and induces cell death
of renal carcinoma cells providing preclinical evidence for a pairwise combination
of these anticancer drugs as a rational strategy to improve renal cancer treatment
Domaines
Sciences du Vivant [q-bio]Origine | Publication financée par une institution |
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