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This is a combination therapy consisting of **CYH33**, a highly selective small molecule inhibitor of phosphatidylinositol 3-kinase alpha (PI3Kα), **fulvestrant**, a selective estrogen receptor degrader (SERD), and **palbociclib**, a small molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6). CYH33 directly inhibits the PI3Kα isoform, blocking a critical node in tumor cell growth, survival, and metabolism, especially in tumors with PIK3CA mutations. Fulvestrant binds to the estrogen receptor and accelerates its degradation, antagonizing estrogen signalling in hormone receptor-positive breast cancers. Palbociclib inhibits CDK4/6, arresting cell cycle progression at the G1 phase, and is used in combination with hormonal therapy for hormone receptor-positive, HER2-negative breast cancer. Together, the combination aims at synergistic antitumor effects by attacking both the PI3K pathway and by blocking hormonal and cell cycle signalling.
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