In 1971, Dr Judah Folkman published the “angiogenic hypothesis” suggesting that
ID: 96337 • 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 mediated signalling has been shown to be actively engahed in multiple cellular signals including tumorigenesis and hypoxia. According to the information, VEGF oversecretion mediates angiogenesis and helps in progressive generation of tumor. Here, two selective approaches can be utilized to prevent VEGF-mediated signalling:
1. Since VEGF signalling is modulated by specific surface receptors, blocking these receptors with candidate pharmacophores can directly prevent downstream VEGF signalling, hence preventing tumor growth.
2. The siRNA mediated tissue-specific silencing of VEGF gene might also help in preventing VEGF-mediated signalling.
Together, these two approaches can help in preventing VEGF-mediated angiogenesis and tumor growth in cancer and hypoxia without causing any adverse side effect on other cells/tissues.