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This combination therapy consists of sorafenib, a multikinase inhibitor, and letrozole, a non-steroidal aromatase inhibitor. Sorafenib targets multiple receptor tyrosine kinases, including vascular endothelial growth factor receptors (VEGFR-1, -2, and -3), platelet-derived growth factor receptor beta (PDGFR-beta), and the Raf/MEK/ERK signaling pathway, thereby inhibiting tumor cell proliferation and angiogenesis. Letrozole works by blocking the aromatase enzyme, which is responsible for the conversion of androgens to estrogens, effectively lowering estrogen levels in postmenopausal women. This combination was evaluated by Rutgers, The State University of New Jersey, in a Phase I/II clinical trial (NCT00634634) for the treatment of postmenopausal women with hormone receptor-positive (ER+) locally advanced or metastatic breast cancer, with the goal of determining if the addition of an anti-angiogenic agent could improve outcomes or delay endocrine resistance.
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