Description
BYL-719 is an ATP-competitive oral PI3K inhibitor selective for the p110α isoform that is activated by a mutant PIK3CA gene in HER2+ breast cancers and gastric cancers. BYL-719 exhibits anticancer chemotherapeutic activity and inhibits proliferation in a variety of cell lines. IGF1 and neuregulin 1 activate mTOR, a downstream target of PI3K that mediates resistance to BYL-719 in some in vitro cancer models. This compound also decreases invasion and epithelial-to-mesenchymal transition (EMT) in cellular and animal models of squamous cell lung cancer.
References
Bonelli MA, Cavazzoni A, Saccani F, et al. Inhibition of PI3K pathway reduces invasiveness and epithelial-to-mesenchymal transition in squamous lung cancer cell lines harboring PIK3CA gene alterations. Mol Cancer Ther. 2015 May 26. [Epub ahead of print]. PMID: 26013318.
Elkabets M, Vora S, Juric D, et al. mTORC1 Inhibition Is Required for Sensitivity to PI3K p110α Inhibitors in PIK3CA-Mutant Breast Cancer. Sci Transl Med. 2013 Jul 31;5(196):196ra99. PMID: 23903756.
Abstract: Juric. BYL719, a next generation PI3K alpha specific inhibitor: Preliminary safety, PK, and efficacy results from the first-in-human study. American Association for Cancer Research. 2012.
