More than 60% of breast cancers harbor genomic changes in the PI3K-AKT-mTOR, or phosphatidylinositol-3-kinase/AKT/mechanistic target of rapamycin, pathway, but attempts to develop drugs that target components in the pathway have been largely unsuccessful. Potentially hundreds of clinical trials have failed, but scientists haven’t really understood why. Researchers headed by a team at the University of California, San Francisco (UCSF), have now used a new unbiased chemoproteomics technique to identify an unrelated protein, Aurora kinase A (AURKA), which effectively acts to protect cancer cells from PI3K pathway-targeted drugs. Their in vitro and in vivo studies showed that treating cancer using the FDA-approved PI3K pathway component inhibitor everolimus in combination with a Phase II-stage experimental AURKA inhibitor stopped the growth of estrogen receptor-positive t umors and also killed cancer cells. There have been more than 200 clinical trials with experimental drugs that target the PI3K pathway, and probably more ...
Original Article: Path for Embattled Breast Cancer Drugs Cleared by One Protein Inhibitor