No, it binds to phosphatidylserine exposed on the surface of cells. This normally occurs when cells are undergoing apoptosis or stressed. It turns out that many tumor cells have increased PS on their surface. More importantly, the otherwise healthy endothelial cells associated with the tumor bed are somehow induced to up-regulate PS, I am not aware of why this happens, but outside of the tumor these cells do not express significant levels of PS. The important thing is that Bavituximab stimulates ADCC by innate cells, not only killing them, but also setting off an immune response through inflammatory cytokine release. So, in addition to targeting tumor cells, it should be anti-angiogenic. Blocking signaling molecules appears to have limited efficacy in cancer therapy. Herceptin, for example, does not act by blocking the Her2 receptor function, it acts by inducing ADCC and attempts to manipulate signaling in tumor cells using small molecules has been largely unfruitful so far.
DALLAS – Sept. 18, 2013 – Overactivity of a protein that normally cues cells to divide sabotages the body’s natural cellular recycling process, leading to heightened cancer growth and chemotherapy resistance, UT Southwestern Medical Center researchers have found.
The epidermal growth factor receptor, or EGFR, is found at abnormally high levels on the surface of many types of cancer cells. The study, led by Dr. Beth Levine and published Sept. 12 in Cell, revealed that EGFR turns off autophagy, a process by which cells recycle unneeded parts, by binding to a protein, Beclin 1, which normally turns on the process. The researchers found that the deactivation of autophagy by EGFR led to more rapid tumor growth and chemotherapy resistance in mice implanted with non-small lung carcinoma cells.
“The fact that this type of cell surface receptor can directly interact with Beclin 1 and shut off autophagy provides fundamental insight into how certain oncogenes may cause cancer,” said Dr. Levine, director of the Center for Autophagy Research and a Howard Hughes Medical Institute (HHMI) investigator at UT Southwestern. “Our findings suggest that inactivation of autophagy may be a critically important factor in the progression of lung cancer.”
Earlier work in the laboratory of Dr. Levine identified beclin 1 as the first mammalian gene shown to function in autophagy. Defects in this gene may contribute not only to cancer, but also to aging, neurodegenerative diseases, and infectious diseases.