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SHR8443 is an orally bioavailable, highly selective small-molecule inhibitor of the alpha isoform of phosphatidylinositol 3-kinase (PI3Kα), which is encoded by the PIK3CA gene. Developed by Jiangsu Hengrui Pharmaceuticals, SHR8443 is designed to target the PI3K/AKT/mTOR signaling pathway, a pathway frequently dysregulated in various cancers due to PIK3CA mutations or amplifications. In the context of hormone receptor-positive (HR+), HER2-negative advanced breast cancer, SHR8443 is being evaluated in a Phase II precision medicine platform study (NCT05511012) led by Fudan University. This study utilizes SNF (Similarity Network Fusion) molecular subtyping to assign patients to targeted therapies, with SHR8443 specifically targeting the SNF4 subtype characterized by PI3K pathway activation. By inhibiting PI3Kα, SHR8443 aims to overcome resistance to endocrine therapy and inhibit tumor cell proliferation and survival.
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