foretinib + lapatinib

Foretinib + lapatinib is a combination drug consisting of two small molecule tyrosine kinase inhibitors targeting different receptors involved in cancer cell growth and survival. Foretinib inhibits multiple receptor tyrosine kinases including c-Met (hepatocyte growth factor receptor), VEGF receptor 2, PDGFRB, AXL, FLT3, TIE-2, RET and RON kinases. Lapatinib is an inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). The combination aims to block both EGFR/HER2 and MET pathways to overcome resistance mechanisms in cancers such as HER-2 positive metastatic breast cancer and triple-negative breast cancer (TNBC). This dual inhibition reduces tumor cell viability, proliferation, migration, invasion and induces cell cycle arrest at G2/M phase. The combination has shown synergistic cytotoxic effects in various cancer cell lines including breast cancer and melanoma. Clinical studies have established recommended phase II doses with foretinib at 45 mg once daily orally combined with lapatinib at 1000 mg once daily orally. Limited clinical activity was observed in a predominantly unselected cohort of HER-2 positive metastatic breast cancer patients[1][2][3][4].