An experimental drug already shown to be safe and to help some patients with clear cell renal cell carcinoma (ccRCC), a deadly form of kidney cancer, effectively disables its molecular target. The finding from a team of researchers at the UT Southwestern Medical Center’s Kidney Cancer Program, was published in the February 14, 2020 issue of Clinical Cancer Research, reveals a weakness in this cancer that could be further exploited with other targeted treatments in the future. The article is titled “HIF-2 Complex Dissociation, Target Inhibition, and Acquired Resistance with PT2385, a First-in-Class HIF-2 Inhibitor, in Patients with Clear Cell Renal Cell Carcinoma.” Approximately 70,000 new cases of ccRCC are diagnosed every year in the U.S. The five-year life expectancy after diagnosis is low compared with other cancers, at about 10-12 percent. Unlike many other forms of cancer, ccRCC doesn’t respond to chemotherapy or conventional radiation. When study lead author James Brugarolas, MD, PhD, Professor of Internal Medicine (Hematology/Oncology) and Director of the Kidney Cancer Program at UT Southwestern, began his career two decades ago, only one medication was approved to treat this cancer. There are now over a dozen approved drugs for ccRCC; however, says Dr. Brugarolas, each offers only a modest effect on survival and comes with a host of side effects. Searching for better pharmaceuticals to fight this cancer, researchers at the Kidney Cancer Program focused on a protein known as hypoxia-inducible factor 2α (HIF-2α), which investigators at UTSW first discovered and described in the late 1990s. HIF-2α is a target of a tumor suppressor protein called von Hippel-Lindau (VHL) protein that’s characteristically inactivated in most cases of ccRCC.
Login Or Register To Read Full Story