Therapeutics: Phosphoinositide 3-kinase (PI3K) α; PI3K catalytic subunit α polypeptide (PIK3CA; p110α)

In vitro and mouse studies suggest combining PI3Kα inhibitors with estrogen receptor antagonists could help treat PI3K-mutant breast cancers. In estrogen receptor-expressing human breast cancer cell lines with activating PIK3CA mutations, a PI3Kα inhibitor increased expression of estrogen receptor mRNA and protein, and expression of estrogen receptor target genes compared with vehicle. In mice with estrogen receptor-positive, PIK3CA-mutant xenograft breast tumors, the PI3Kα inhibitor BYL719 plus the estrogen receptor antagonist fulvestrant synergistically decreased tumor growth compared with either treatment alone. Next steps could include testing the combination in additional breast cancer models.

Novartis AG has BYL719 in Phase III testing to treat breast cancer and Phase I/II testing for head and neck cancer and solid tumors...