Onartuzumab

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Onartuzumab is a monoclonal antibody designed for the treatment of cancer. It specifically targets the MET receptor, which is often implicated in various types of cancer, including lung cancer and gastric cancer. Onartuzumab works by inhibiting the hepatocyte growth factor (HGF) from activating the MET receptor, thereby preventing the downstream signaling pathways that lead to tumor growth and metastasis.

Development and Clinical Trials

Onartuzumab was developed by Genentech, a subsidiary of Roche. It was initially considered a promising therapeutic agent due to its novel mechanism of action. Clinical trials were conducted to evaluate its efficacy in treating various cancers, particularly non-small cell lung cancer (NSCLC) and gastric cancer.

However, the results from these trials were disappointing. The Phase III trial in NSCLC patients, known as the METLung study, did not meet its primary endpoint of improving overall survival in patients treated with onartuzumab in combination with erlotinib compared to those treated with erlotinib alone. Similar outcomes were observed in trials involving patients with gastric cancer.

Mechanism of Action

Onartuzumab binds to the MET receptor, a tyrosine kinase receptor that is overexpressed or mutated in many types of tumors. By blocking the interaction between MET and its ligand, HGF, onartuzumab inhibits the receptor's ability to activate and trigger signaling pathways that promote cell proliferation, survival, and migration.

Regulatory Status

Following the failure to demonstrate a significant clinical benefit in major trials, the development of onartuzumab for lung and gastric cancers was discontinued. As of the last update, onartuzumab has not been approved by any regulatory agency for the treatment of cancer.

Future Directions

Research continues in the field of MET inhibitors, with other candidates and approaches being explored to target the MET/HGF pathway. The lessons learned from the development of onartuzumab are being used to better understand the complexities of targeting receptor tyrosine kinases in cancer therapy.

See Also

• Monoclonal antibodies for cancer
• Cancer treatment
• Targeted therapy
• Receptor tyrosine kinase inhibitors