BMS-754807 + letrozole

BMS-754807 + letrozole is a combination of a dual IGF-1R/InsR tyrosine kinase inhibitor (BMS-754807) and a non-steroidal aromatase inhibitor (letrozole) developed for the treatment of hormone-sensitive, estrogen receptor-positive breast cancer, particularly where resistance to endocrine therapy is a concern. BMS-754807 blocks insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (InsR, especially isoform A), targeting pathways that contribute to therapy resistance and cell proliferation. Letrozole inhibits the aromatase enzyme, decreasing estrogen production and thus the growth stimulus for ER+ tumors. Preclinical and early clinical studies have shown that the combination is synergistic, resulting in greater tumor regression and antiproliferative effects than either agent alone, without notable added toxicity[1][3][5][4].