fulvestrant + hs-10352

Fulvestrant + HS-10352 is a combination therapy being investigated for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer harboring PIK3CA mutations. HS-10352 is a highly potent and selective small molecule inhibitor of phosphoinositide 3-kinase alpha (PI3Kα/p110α) with an IC50 value of 0.34 nM. It exhibits 321-fold, 103-fold, and 159-fold higher selectivity for PI3Kα over PI3Kβ, PI3Kδ, and PI3Kγ, respectively. This heightened selectivity may help minimize severe side effects commonly associated with inhibition of other PI3K isoforms. Fulvestrant is an estrogen receptor antagonist administered intramuscularly. The combination shows synergistic anticancer effects, as fulvestrant can enhance the sensitivity of estrogen receptor-positive tumors to PI3Kα inhibition.