GDC-0980 + fulvestrant

GDC-0980 + fulvestrant is a combination therapy under investigation for the treatment of advanced or metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer resistant to aromatase inhibitors. **GDC-0980 (apitolisib)** is a potent, selective, orally bioavailable **small molecule inhibitor** targeting class I phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR). It disrupts PI3K/AKT/mTOR signaling, a pathway often deregulated in cancers, leading to inhibited tumor cell growth, survival, and proliferation[3][4][2]. **Fulvestrant** is a selective estrogen receptor downregulator (SERD) that binds competitively to estrogen receptors, leading to receptor degradation and inhibition of estrogen-driven tumor growth. The rationale for this combination is to target both hormonal signaling (ER) and cell proliferation/survival signaling (PI3K/mTOR), two pathways known to drive resistance mechanisms in advanced breast cancer[5][7][1]. Clinical trials have tested the combination (30 mg oral apitolisib daily plus standard fulvestrant dosing), but the apitolisib arm was discontinued in at least one study due to high rates of grade 3 toxicities[7]. The combination remains investigational and is not approved for any indication.

Other names

apitolisib + fulvestrant