Dr. Hutson on Challenges With Targeted Therapy in Non-Clear Cell RCC

Thomas Hutson, DO, PharmD, director, Urologic Oncology Program, co-chair, Urologic Cancer Research and Treatment Center, Baylor University Medical Center, professor of medicine, Texas A&M College of Medicine, discusses challenges with targeted therapy in non-clear cell renal cell carcinoma (RCC).

Non-clear cell RCC subtypes have individual natural histories, their own responses to various therapies, and their own genetic abnormalities, says Hutson.

 Notably, the Von Hippel-Lindau (VHL) gene, which was discovered in the 1990s, is commonly mutated. Loss of function in VHLresults in increased uptake of hypoxia-inducible factor (HIF) and downstream increase of VEGF, Hutson explains. Ultimately, the discovery of VHL led to the development of targeted therapies, such as sunitinib (Sutent), lenvatinib (Lenvima), and cabozantinib (Cabometyx) in clear cell RCC.

However, VHL mutations are not oncogenic drivers in non-clear cell RCC. Instead, non-clear cell histologies are associated with other abnormalities, such as c-MET in papillary RCC and fumarate hydratase deficiency in papillary type 2 RCC. As such, there is a significant need to develop additional targeted therapies for patients with non-clear cell RCC, Hutson concludes.