In 1971, Dr Judah Folkman published the “angiogenic hypothesis” suggesting that
ID: 97345 • Letter: I
Question
In 1971, Dr Judah Folkman published the “angiogenic hypothesis” suggesting that a tumor cannot grow beyond 1–2 millimeters without the development (angiogenesis) of new blood vessels that provide access to oxygen and nutrients. During the 1990s, it was discovered that vascular endothelial growth factor (VEGF) stimulates the proliferation and migration of the cells that form blood vessels, leading to the formation of new blood vessels. VEGF binds to receptor tyrosine kinases (RTKs) on the cell surface and causes the RTKs to dimerize and become active, thereby initiating an intracellular signaling cascade that stimulates cell division and inhibits apoptosis. Many cancer cells secrete high levels of VEGF. Increased VEGF expression in a tumor is correlated with a poor medical outcome for the patient. Some evidence suggests that blocking VEGF-dependent signaling may prevent the formation of new blood vessels and lead to the death of immature blood vessels without disturbing mature blood vessels. You work for a biotechnology company that seeks to create anticancer drugs that prevent the growth of tumors and/or cause tumors to shrink, while leaving normal cells relatively untouched. After learning about VEGF, you have a bright idea for a new mechanism of action for a potential anticancer drug. What is your idea?
Explanation / Answer
VEGF signalling should be inhibited to stop angiogenesis. One hitch to this treatment is that this would lead to lowering of NO in the endothelial cells causing hypertension. Hence to avoid this, one would have to develop a drug delivery system such that it could be released only in the vicinity of the tumour (eg. in vesicles coated with antibodies against a cancer cell-specific surface marker) or try to develop a drug against a candidate protein downstream of VEGF but not involved in regulating NO levels ( for eg. a protein involved in AKT pathway).