LY3023414 + fulvestrant

LY3023414 + fulvestrant is a combination therapy under investigation for the treatment of advanced hormone receptor-positive (HR+), HER2-negative breast cancer. LY3023414 is an oral, potent, and selective ATP-competitive inhibitor targeting class I phosphatidylinositol 3-kinase (PI3K) isoforms, mammalian target of rapamycin (mTOR), and DNA-dependent protein kinase (DNA-PK). Fulvestrant is a selective estrogen receptor degrader (SERD) that binds to and accelerates degradation of the estrogen receptor, thereby inhibiting estrogen signaling. The rationale for combining these agents lies in targeting both the PI3K/mTOR pathway—frequently activated in breast cancer—and hormone signaling pathways to overcome resistance mechanisms and improve antitumor efficacy. This combination has been evaluated in early-phase clinical trials for patients with advanced HR+, HER2- breast cancer who are refractory to standard treatments[1][6].