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A combination of **palbociclib**, a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, and **bosutinib**, a dual Src and Abl tyrosine kinase inhibitor. This combination is under investigation for metastatic hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer, particularly in patients resistant to prior aromatase inhibitors and CDK4/6 inhibitors. Palbociclib blocks cell cycle progression at the G1 phase by inhibiting CDK4/6, leading to RB protein hypophosphorylation and cell cycle arrest. Bosutinib inhibits the Src/Abl pathway, potentially overcoming acquired endocrine resistance by targeting mechanisms associated with cancer cell proliferation and survival. This combination seeks to address resistance mechanisms and improve outcomes for patients with advanced breast cancer[2][3][4][7][5][9].
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