INTRODUCTION
breast cancer, cancer, Breast cancer, gastric cancer HGC‐27, human gastric cancer, deaths, tumors, weight loss
BREAST CANCER, PROLIFERATION, CANCER, BREAST CANCER, TUMOR GROWTH, TUMORS
Breast cancer is the most common cancer and the leading cause of cancer‐related deaths in females.HS‐10352 is a novel, highly selective PI3Kα inhibitor with an IC50 value of 0.34 nM. It exhibits far greater selectivity for PI3Kα over PI3Kβ, PI3Kδ, and PI3Kγ, with 321‐, 103‐, and 159‐fold higher selectivity, respectively. This heightened selectivity may help minimize the severe side effects commonly associated with the inhibition of PI3Kβ, δ, and γ. Preclinical studies, both in vitro and in vivo, have demonstrated that HS‐10352 effectively inhibits PIK3CA mutations. For instance, HS‐10352 substantially inhibited the proliferation of human breast cancer cell lines harboring PIK3CA mutations, such as HCC1954 and MCF‐7, in vitro assays. Conversely, HS‐10352 displayed no inhibitory effects on cell lines lacking PIK3CA mutations, like the human breast cancer HDQ‐P1 cell line and the human gastric cancer SNU‐1 and MKN‐74 cell lines. In animal models, HS‐10352 markedly suppressed the growth of transplanted tumors in a dose‐dependent manner in mice bearing gastric cancer HGC‐27 (PIK3CA E542K) and human breast cancer HCC‐1954 (PIK3CA H1047R) tumors. Specifically, in mice with HCC‐1954 tumors, oral treatment with HS‐10352 at 10 mg/kg once‐daily (QD) for 21 days resulted in a 124.47% inhibition in tumor growth without causing significant weight loss.This study aimed to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor efficacy of oral HS‐10352 in patients with HR‐positive, HER2‐negative ABC.