In 1971, Dr Judah Folkman published the “angiogenic hypothesis” suggesting that
ID: 174993 • 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. propose different strategies to develop a potential anticancer drug.
Explanation / Answer
Anticancer drugs are developed to inhibit the angiogenesis in tumors to control the tumor growth. These anticancer drugs act by different mechanisms. When the tumors become 1 to 2mm in size, then tumors induce blood vessel formation or angiogenesis by producing a protein called vascular endothelial growth factor (VEGF). This VEGF protein attaches to receptors on cells that line the walls of blood vessels within the tumour and helps in tumor growth.
Anticancer drugs targeting VEGF protein: Some drugs can block vascular endothelial growth factor (VEGF) from binding to the receptors on the cells that line the blood vessels. This inhibits the growth of blood vessels.
Anticancer drugs that block signalling within the cells: Some drugs inhibit the VEGF receptors from sending growth signals into the blood vessel cells. These anticancer drugs are also known as cancer growth blockers or tyrosine kinase inhibitors (TKIs). Sunitnib is a TKI that inhibit the growth signals in blood vessels.
Anticancer drugs affecting the signalling between cells: Some anticancer drugs play a key role in cellular communication. These act on the chemicals signals used by the cells to stimulate and signal for growth of each other. As the signalling is inhibited, it may result in blocking the formation of blood vessels. Anticancer drugs inhibiting the cellular signalling include thalidomide and lenalidomide (Revlimid).