Large Genomic Study Finds New Kidney Cancer Subtypes and Drug Targets

March 15, 2016
Large Genomic Study Finds New Kidney Cancer Subtypes and Drug Targets
A comprehensive molecular analysis of 894 primary renal cell carcinomas resulted in nine subtypes defined by systematic analysis of five genomic data platforms. Each major histologic types represent substantial molecular diversity. Presumed actionable alterations include PI3K and immune checkpoint pathways. [Dr. Chad Creighton/Cell Reports]

A new collaborative study led by researchers at Baylor College of Medicine has not only helped to restructure the taxonomy of kidney cancer, it has also uncovered some new actionable therapeutic targets. The new study was a comprehensive molecular analysis of almost 900 kidney cancer cases that found substantial molecular diversity within each major histological type that pathologists typically use to categorize cancer.

Using data from The Cancer Genome Atlas, the investigators uncovered that what has historically been considered three major types of kidney cancer according to microscopic morphology could be further distinguished into nine major subtypes through molecular analyses. Moreover, each subtype was unique regarding altered molecular pathways and patient survival.      

The researchers hope that their findings will help pave the way for more effective personalized medicine. Understanding what makes each kidney cancer unique can provide clues to finding targets for effective therapies, and the nine subtypes the research team uncovered were found to have therapeutic implications.

"Different types of cancer can show different pathways being dysregulated," noted senior study author Chad Creighton, Ph.D., associate professor of medicine and member of the Dan L Duncan Comprehensive Cancer Center Division of Biostatistics at Baylor College of Medicine. "And for some of the pathways, we have therapies we can use to target them."

The findings from this study were published recently in Cell Reports in an article entitled “Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma.”

“We classified 894 renal cell carcinomas (RCCs) of various histologic types into nine major genomic subtypes,” the authors wrote. “Site of origin within the nephron was one major determinant in the classification, reflecting differences among clear cell, chromophobe, and papillary RCC. Widespread molecular changes associated with TFE3 gene fusion or chromatin modifier genes were present within a specific subtype and spanned multiple subtypes.”

Interestingly, the scientists found that the immune checkpoint pathway was most active in a subtype of clear cell kidney cancer that is typically very aggressive. The immune checkpoint pathway can potentially be a target for specific therapies.

"Not all patients have this pathway activated, but molecular analysis would allow us to identify those patients that represent the best candidates for receiving therapies that target that pathway specifically," Dr. Creighton explained. "If we have this information, then we may have an idea of what would work better for the patient. The molecular information can potentially help guide better decisions for treating each patient."

The researchers were excited by the results of their extensive analysis and hope that their data will be used extensively by investigators in the field to continue advancing their studies of kidney cancer.

"Much is going to be learned about kidney cancer with researchers using these data to answer new questions about the disease," Dr. Creighton stated.