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Improved Understanding of Renal Cell Cancer Mutations and Identification of Biomarkers May Inform Future Treatment Options

January 15, 2019

Daniel M. Geynisman, MD. Phillip Abbosh, MD, PhD, assistant professor in the Molecular Therapeutics Program, and Christopher D'Avella, MD, a hematology/oncology fellow at Fox Chase, contributed to the paper.Daniel M. Geynisman, MD. Phillip Abbosh, MD, PhD, assistant professor in the Molecular Therapeutics Program, and Christopher D'Avella, MD, a hematology/oncology fellow at Fox Chase, contributed to the paper.

PHILADELPHIA (January 15, 2019) — While renal cell cancer (RCC) treatments have improved as researchers gained a deeper understanding of the disease’s genetics and genomics, there is an opportunity to make a greater difference by identifying biomarkers and mutations that will help oncologists select the most effective treatments for individual patients, according to a recent paper by Daniel M. Geynisman, MD, Fox Chase Cancer Center.

The review article, entitled, “Mutations in renal cell carcinoma,” was published in the November 2018 edition of Urologic Oncology: Seminars and Original Investigations. Phillip Abbosh, MD, PhD, assistant professor in the Molecular Therapeutics Program, and Christopher D'Avella, MD, a hematology/oncology fellow at Fox Chase, contributed to the paper.

“There have been many strides in treating RCC but future studies should explore linking genetics to prognosis, resistance to targeted therapies, and the identification of future therapeutic targets,” said Geynisman.

In the past, RCC treatments were limited, and had a high-toxicity profile and low response rate. However, targeted therapy and immunotherapy options are now available because of the increased understanding of the molecular basis of RCC.

The paper listed several highlights found in RCC molecular research:

  • Frequent inactivation of the Von Hippel Lindau gene in ccRCC led to the development of vascular endothelial growth factor and mammalian target of rapamycin inhibitors.
  • Genomic sequencing of ccRCC tumors identified other common mutations such as BAP-1, PBRM1, SETD2, and PIK3CA.
  • Papillary RCC has shown a high level of mutations in the MET gene, and early clinical data suggests the utility of MET targeted therapy.
  • Rarer sarcomatoid tumors show mutations in TP53 and NF2 that may be important to their development.

RCC comprises 80-85 percent of all renal neoplasms, and is estimated to represent 3.8 percent of all new cancer diagnoses in the United States. In 2017, there were 63,990 new cases of RCC and 14,400 deaths from the disease. The most common form of RCC is clear cell RCC (ccRCC), followed by papillary RCC and chromophobe RCC subtypes.

       

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