“We have identified candidate drug targets that have been explored in other cancer types, but have yet to be evaluated in ccRCC.”

 The most prominent form of kidney cancer is clear cell renal cell carcinoma (ccRCC), and Hopkins investigators are part of a team that has delineated the molecular profiles of ccRCC. The work, done as part of the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium initiative, was published in Cell. The paper’s first author was David Clark, Ph.D., a postdoctoral fellow in the lab of Hui Zhang, M.S., Ph.D., Director of the Mass Spectrometry Core Facility in the Center for Biomarker Discovery and Translation.

Not only did the team identify several novel aspects of ccRCC biology, but “this represents the first major, large-scale proteogenomic characterization of ccRCC,” explains urologist and clinical collaborator Phillip Pierorazio, M.D. “Many of the genetic alterations of kidney cancer are known, but this research demonstrates how those genetic alterations trickle down to proteins and active functions of the cells that define a kidney cancer.” The implications of this research are exciting, he adds: “It tells us much more about potential targets for diagnosis and therapy than we previously knew.”

Although many patients have the same type of cancer, there are many variations at the genomic level – tiny, subtle differences that can affect how well someone responds to treatment. In this study, Clark and colleagues showed that “protein features could be leveraged to stratify patients into specific, targeted treatment regimens that could be more effective,” says medical oncologist Yasser Ged, M.B.B.S. “Some of these tumors progress down a pathway of vascular growth factors, some progress by manipulating the immune system – and some take advantage of a combination of vascular growth factors and the immune system. Fortunately, we have medications to target vascular growth factors and the immune system. Data from this study may help us understand how to personalize treatment – to couple or uncouple those therapies, as needed.”

In addition, the team discovered “cellular switches,” called kinases, that contribute to kidney cancer cell growth and the corresponding protein regulators. Even more exciting: “There are known, FDA-approved inhibitors for these kinases,” says Clark, “and we have identified candidate drug targets that have been explored in other cancer types, but have yet to be evaluated in ccRCC. We hope this work will expand the repertoire of treatments for our patients.”