onartuzumab + 5-fluorouracil + folinic acid + oxaliplatin

Onartuzumab + 5-fluorouracil + folinic acid + oxaliplatin is a multi-agent combination regimen used for investigational oncology therapy, primarily targeting advanced and metastatic solid tumors. This combination brings together: - **Onartuzumab**: a humanized monovalent monoclonal antibody selectively targeting the hepatocyte growth factor receptor (**MET**). Onartuzumab blocks the binding of its natural ligand hepatocyte growth factor (**HGF**), antagonizing MET signaling cascades (Gab1, Akt, ERK, 70-S6K), which regulates tumor cell proliferation, survival, and migration[1][2][3][4]. - **5-Fluorouracil (5-FU)**: a pyrimidine analog antimetabolite that inhibits thymidylate synthase, blocking DNA synthesis and leading to apoptosis of rapidly dividing tumor cells. - **Folinic acid (leucovorin)**: enhances cytotoxicity of 5-fluorouracil by stabilizing thymidylate synthase binding, increasing antitumor effects. - **Oxaliplatin**: a third-generation platinum-based chemotherapeutic, forming DNA crosslinks and triggering apoptosis in tumor cells. The regimen is primarily used experimentally in colorectal, gastric, and other gastrointestinal cancers where MET signaling is implicated. Onartuzumab introduces targeted therapy to the cytotoxic backbone of 5-FU, folinic acid, and oxaliplatin, aiming for synergy against MET-driven resistance and disease progression[2][4].