alpelisib + palazestrant

Alpelisib + palazestrant is an investigational combination therapy consisting of alpelisib, a selective PI3K alpha inhibitor, and palazestrant, an oral selective estrogen receptor degrader (SERD). Alpelisib inhibits the phosphatidylinositol 3-kinase alpha (PI3Kα) isoform, blocking the PI3K/AKT/mTOR signaling pathway that is frequently activated in cancers with PIK3CA mutations. Palazestrant targets and degrades the estrogen receptor (ER), thereby inhibiting ER-driven tumor growth. This combination aims to overcome resistance mechanisms in hormone receptor-positive, HER2-negative advanced or metastatic breast cancer by simultaneously targeting two key pathways involved in tumor proliferation and survival.