letrozole + pazopanib

Letrozole + pazopanib is an investigational combination therapy consisting of two small molecule drugs with distinct mechanisms of action. Letrozole is a nonsteroidal aromatase inhibitor that suppresses estrogen biosynthesis, thereby reducing estrogen-driven tumor growth in hormone receptor-positive cancers. Pazopanib is a second-generation multitargeted tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptors (VEGFR-1, -2, -3), platelet-derived growth factor receptors (PDGFRA and PDGFRB), and c-Kit, inhibiting angiogenesis and tumor proliferation. This combination has been studied primarily in postmenopausal women with hormone receptor-positive advanced breast cancer resistant to prior nonsteroidal aromatase inhibitors[1][2]. The rationale for the combination is based on evidence that increased VEGF signaling may contribute to resistance against endocrine therapies like letrozole; thus, dual inhibition may improve clinical outcomes[1].