Researchers at Lineberger Comprehensive Cancer Center in University of North Carolina revealed a therapeutic target for kidney cancers that share a common genetic change. The researchers knew prior to their study that this genetic change can form plenty of blood vessels that feed tumors and support their survival. Genetic changes that lead to a loss-of-function in a tumor suppressor gene is present in 90 percent of the most common type of kidney cancers. In the study published in journal Science, researchers were able to identify a downstream effect of this particular genetic change that is aiding in kidney cancer formation. In particular, they discovered a protein called ZHX2, this protein over-accumulates in kidney cancer cells and helps to activate other signals involved in cancer growth. The findings suggest that ZHX2 may serve as a potential new therapeutic target for drug development in tretaing clear cell renal cell carcinoma; the most common type of kidney cancer. "If you lose VHL (a tumor suppressor gene), you will accumulate lots of this ZHX2 protein, which will turn on signals that promote kidney cancer," said UNC Lineberger's Qing Zhang, PhD, an assistant professor in the UNC School of Medicine Department of Pathology & Laboratory Medicine and Pharmacology. "This protein could be a potential therapeutic target used to treat kidney cancer on its own or in combination. The next step is to try to figure out how we can target it therapeutically."
Renal cell clear cell carcinoma is responsible for about 70 percent of all kidney cancer cases and about 90 percent of patients diagnosed with clear cell renal cell carcinoma have mutations that lead to the loss-of-function of VHL. When VHL loses its function, blood vessels are triggered to grow. "VHL is the most important tumor suppressor in clear cell renal cell carcinoma," Zhang said. "There are extensive reports showing that from initiation to tumor progression to metastasis -- during the whole process of kidney cancer development -- VHL plays a central role. It is important to understand how the VHL loss contributes to kidney cancer, and how we can therapeutically target the downstream effects of this loss in kidney cancer. We wanted to understand, once VHL is lost, what else in kidney cancer cells is promoting oncogenesis?" Zhang said. "Therapeutically speaking, we're trying to understand how we can target these novel signaling pathways, once we identify them."
UNC Lineberger's William Kim, MD, explains that there has been major advances in treating kidney cancer that include molecularly-targeted therapies and immune-based treatments. But, new treatments are needed for patients with the metastatic form of the disease. "The vast majority of kidney cancers have mutations in VHL, so it makes it a very important gene to investigate," said Kim, who is an associate professor of medicine and genetics in the UNC School of Medicine. "In the last decade or more, we've had quite a number of major treatment advances in kidney cancer. There are nearly a dozen FDA-approved treatments now for this disease, but many of them are similar. Studies like this are important because they delineate the underlying biology of kidney cancer and identify novel, distinct pathways to develop drugs against."
Source: UNC Lineberger Comprehensive Cancer Center
