In 1971, Dr Judah Folkman published the “angiogenic hypothesis” suggesting that
ID: 91250 • 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
The new drug can be designed to inhibit the binding of VEGF to the tyrosine kinase receptors. Since tyrosine kinase receptor stimulation by VEGF leads to inhibition of apoptosis and formation of new blood vessels, drugs that block these receptors will prevent formation of new blood vessels. This will selectively affect tumor cells which utilise new blood vessels without affecting the functioning of normal cells which utilise mature blood vessels.