Therapeutics: Estrogen-related receptor α (ERR-α; ESRRA; NR3B1); phosphoinositide 3-kinase (PI3K); mammalian target of rapamycin (mTOR; FRAP; RAFT1)

Cell and mouse studies suggest combining inhibitors of ERR-α with inhibitors of PI3K or PI3K/mTOR could help treat triple-negative breast cancer (TNBC). In a human TNBC cell line, an ERR-α inhibitor tool compound increased sensitivity to the PI3K inhibitor pictilisib, the dual PI3K/mTOR inhibitor GDC-0980 or the dual PI3K/mTOR inhibitor BEZ235, compared with no ERR-α inhibitor. In a xenograft mouse model of TNBC, the ERR-α inhibitor plus BEZ235 decreased tumor growth compared with either agent alone. Next steps include identifying ERR-α inhibitors and testing them in combination therapies in animal models of cancer.

Roche and its Genentech Inc. unit have pictilisib (GDC-0941; RG7321) in Phase II testing to treat non-small cell lung cancer (NSCLC) and breast cancer, and have GDC-0980 in Phase II testing to treat breast cancer, endometrial cancer, non-Hodgkin's lymphoma (NHL), renal cancer and solid tumors and Phase I/II testing to treat prostate cancer...