Donald M. McDonald, MD, PhD, a professor in the Department of Anatomy and an investigator in the Cardiovascular Research Institute at the University of California, San Francisco, Comprehensive Cancer Center, discusses how the knowledge of bevacizumab (Avastin) has evolved since it was first approved for metastatic colorectal cancer (mCRC) 7 years ago.

McDonald draws the analogy that while 7 years may seem long that other drugs, such as aspirin, have been in use for 120 years and are still being investigated and fully understood.

The molecular aspects of bevacizumab have not changed and are currently understood, but the overall physiological impact of the drug is still being investigated. The effects on the tumor and the rest of the body from inhibiting angiogenesis by blocking VEGF are becoming bettering understood.

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Dr. Donald McDonald from the UCSF Comprehensive Cancer Center on the Continued Understanding of Bevacizumab

Dr. McDonald on the Continued Understanding of Bevacizumab

Donald M. McDonald, MD, PhD, a professor in the Department of Anatomy and an investigator in the Cardiovascular Research Institute at the University of California, San Francisco Comprehensive Cancer Center, discusses the three approved drugs that inhibit angiogenesis in cancer.

The first drug he mentions is bevacizumab (Avastin), which is a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF). This drug is described as a large-molecule agent and is administered intravenously.

McDonald mentions there are two small-molecule drugs, oral agents, which are also available. The first of the antiangiogenesis agents is sunitinib (Sutent) which is a multi-targeted agent that blocks both VEGF and platelet-derived growth factor (PDGF) receptors. The second small-molecule drug is sorafenib (Nexavar) that also blocks the VEGF and PDGF receptors.

The two small molecule drugs have a higher rate of adverse events because they inhibit multiple pathways.

Dr. Donald McDonald from UCSF Comprehensive Cancer Center Explains Approved Angiogenesis Inhibitors

Dr. McDonald on Approved Angiogenesis Inhibitors

Donald M. McDonald, MD, PhD, a professor in the Department of Anatomy and an investigator in the Cardiovascular Research Institute at the University of California, San Francisco Comprehensive Cancer Center, explains that in the early stages of treatment with angiogenesis inhibitors the sky was believed to be the limit.

It was believed that blocking angiogenesis could stop tumor growth and keep tumors in a dormant state. Some cancers see great benefit, but limitations have become evident, particularly in breast cancer. Overcoming the limitations of inhibiting angiogenesis will be the next research step to take.

Dr. Donald McDonald from the UCSF Comprehensive Cancer Center on the Next Step for Angiogenesis Inhibitors

Dr. McDonald on the Next Step for Angiogenesis Inhibitors

Donald M. McDonald, MD, PhD, a professor in the Department of Anatomy and an investigator in the Cardiovascular Research Institute at the University of California, San Francisco Comprehensive Cancer Center, discusses the recent discovery of novel resistance to therapies that inhibit angiogenesis, particularly in breast cancer.

The underlying mechanisms of anti-angiogenesis resistance are being investigated in pre-clinical trials. Angiogenesis inhibitors prune the blood vessels feeding a tumor causing intratumoral hypoxia. It is believed it is this mechanism that can activate systems that promote invasions and metastasis from the tumor.

At this stage all observations into mechanisms of resistance are from pre-clinical models and it is still unclear how to generalize these studies in human cancers.

Dr. Donald M. McDonald from the UCSF Cancer Center Discusses Resistance to Angiogenesis Inhibitors

Donald M. McDonald, MD, PhD

Articles

Dr. McDonald on the Continued Understanding of Bevacizumab

Dr. McDonald on Approved Angiogenesis Inhibitors

Dr. McDonald on the Next Step for Angiogenesis Inhibitors

Dr. McDonald on Resistance to Angiogenesis Inhibitors