At this year's "96th Annual Meeting of the American Association for Cancer Research (AACR)" held in Anaheim, CA, angiogenesis and its inhibitors generated great interest as a therapeutic approach to treat solid tumors.
Napoleone Ferrara, M.D., described how, in 1989, he discovered a vascular endothelial factor from pituitary glands and developed a humanized monoclonal antibody (bevacizumab/Avastin) to inhibit its activity as a side project at Genentech.
In February 2004, the FDA approved Avastin for marketingthe first antiangiogenesis drug approved by the agency. Avastin is approved for use in combination with 5-fluorouracil as a front-line therapy to treat metastatic colorectal cancers.
In less than a year, Avastin generated product sales of $555 million. Avastin is also in Phase III clinical studies for treating non-squamous, non-small cell lung cancers and metastatic breast cancers. Genentech reported that an interim analysis of the Phase III study demonstrated that Avastin with chemotherapy prolonged disease-free survival in metastatic breast cancer patients.
Last month, Genentech presented Phase III data at ASCO demonstrating that non-small-cell lung cancer patients receiving Avastin with paclitaxel and carboplatin had 30% greater improvement in overall survival than patients just receiving the chemotherapy.
Judah Folkman, M.D., professor of surgery at Children's Hospital (Boston) and cell biology at Harvard University (Cambridge, MA), first proposed the concept of inhibiting vascularization of tumors over 40 years ago to treat solid tumors. He discovered two anti-angiogenic factors, endostatin and angiostatin, which he licensed to EntreMed (Rockville, MD).
However, endostatin is still languishing in the early stages of clinical development as EntreMed refocused its product development strategy to small molecules.
Due to its low toxicity, drug resistance and side effects, monoclonal antibodies are finally fulfilling their promise as anticancer agents. At the time of their discover by Milstein and Kohler in 1975, monoclonal antibodies were thought to be the magic bullet to cure cancer. However, it was over 30 years before biotech companies were able to figure out how to use these reagents in the clinic.
With ImClone's (New York City) Erbitux and Genentech's three approved drugs, biotech companies that are developing monoclonal antibody-based therapeutics are emerging as the key players in oncology.