afuresertib + fulvestrant

Afuresertib + fulvestrant is an investigational combination therapy for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer. Afuresertib (LAE002) is a potent, oral small molecule pan-AKT kinase inhibitor that targets all three AKT isoforms (AKT1, AKT2, and AKT3), disrupting the PI3K/AKT signaling pathway involved in cell survival, proliferation, and resistance to therapy. Fulvestrant is a selective estrogen receptor degrader (SERD) that binds to and accelerates degradation of the estrogen receptor, blocking estrogen-driven tumor growth. The combination aims to overcome resistance mechanisms in HR+/HER2- breast cancer—particularly in patients with PIK3CA/AKT1/PTEN alterations—by simultaneously inhibiting both the AKT pathway and estrogen signaling. Clinical trials have shown promising efficacy with improved progression-free survival compared to fulvestrant monotherapy and a favorable safety profile[2][6][8].