Fighting Kidney Cancer at the Source

William G. Kaelin, Jr., MD, Sidney Farber Professor of Medicine at Harvard Medical School and the Dana Farber Cancer Institute, started work 15 years ago with an interesting bit of information about kidney cancer: patients with a mutation in the VHL gene (von Hippel Lindau syndrome) were much more likely to develop kidney cancer. Kaelin set out to figure out why and possibly
find a treatment for several cancers, including clear-cell renal carcinoma, a deadly form of kidney cancer.

Through his research, Kaelin found that the VHL gene regulates cell response to oxygen levels as well as another molecular factor, HIF, which is responsible for triggering the production of red blood cells and blood vessels based on oxygen supply. Cancer cells with mutated VHL genes can take advantage of this system to trick the body into building blood vessels straight to cancerous tumors, thus feeding their own growth with the body’s blood supply. This mutation in the VHL gene allows the tumor to hijack the HIFs and stimulate the production of the protein VEGF, which enables extra blood vessels to enhance blood supply directly to the tumor.

This discovery led to the production of VEGF inhibitors, which showed success in improving the chances for patients with renal cell carcinoma, a fatal kidney cancer with a median survival of one year. In 2019, Kaelin on two other renown scientists were awarded the Nobel Prize in Physiology or Medicine “for their discoveries of how cells sense and adapt to oxygen availability.”

The link between oxygen and cancer cells continues to be an area of interest for the medical field. Normal cells use HIFs to regulate oxygen supply based on external oxygen availability, but cancer cells use HIFs to increase blood supply and grow tumors. On the other hand, cancer cells without enough oxygen (hypoxic cells) can spread beyond their origin and resist cancer treatments. While it is clear that the use of oxygen (or lack thereof) by cancer cells is tied to cancer growth and treatment, the full story is the subject of ongoing research.

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