ORLANDO, FL The understanding of genetic conditions with predisposition to renal cell cancer is critical for understanding the patients with nonhereditary sporadic kidney cancer and developing better therapies for those patients, according to a presentation at 2017 Genitourinary Cancers Symposium.1

“When we started working on kidney cancer 32 years, kidney cancer was a single disease, but we now that kidney cancer is a number of different types of cancers that just happen to occur this organ with different histologies and different courses,” said W. Marston Linehan, MD, chief of the urologic oncology branch at the National Cancer Institute Center for Cancer Research, Bethesda, Maryland. “We now know of at least 16 different genes that cause kidney cancer and we know of 13 different genes that cause hereditary cancer syndrome.”

Dr Linehan discussed von Hippel-Lindau (VHL) syndrome, one of the most well known genetic conditions associated with hereditary kidney cancer. Patients with this syndrome are at risk increased risk for developing tumors in both kidneys, the adrenal glands, the pancreas, the brain or spine, the eyes, and the inner ears. These tumors are always clear cell kidney cancers.

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Patients with VHL-associated renal carcinoma are managed with active surveillance until the largest renal tumor is 3 cm in diameter. At that time, patients undergo nephron-sparing enucleation. Dr Linehan noted that he has not once had a patient develop metastatic disease when managed in this fashion.

VHL disease results from a mutation in the VHL tumor suppressor gene on chromosome 3. Alterations in this gene have been detected in over 90% of patients with clear cell renal cell carcinoma. These gene mutations are not, however, found in type 1 papillary, type 2 papillary, chromophobe kidney cancer, oncocytoma, collecting duct carcinoma, or renal medullary carcinoma.

VHL gene mutations have downstream effects on VEGF, PDGF, and MET, which regulate angiogenesis, paracrine growth stimulation, and invasion/branching morphogenesis, respectively. This understanding became the foundation of drug development for patients with renal cell carcinoma. Pazopanib, axitinib, lenvatinib, and bevacizumab, for example, target VEGF, while cabozantinib inhibits MET.

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“We are hopeful that by understanding the genetic basis of kidney cancer and knowing that kidney cancer is not 1 but multiple cancers, these cancer disease gene pathways will enable us to improve our diagnosis and certainly improve our management,” said Dr Linehan. “We hope to continue to providing the foundation for the development of effective forms of therapy for every patient with this group of diseases.”


  1. Linehan WM. Genetic conditions with predisposition to renal cell carcinoma. Lecture presented at: 2017 Genitourinary Cancers Symposium; February 16-18, 2017; Orlando, FL.