Minimizing Toxicity While Maintaining Efficacy in RCC - Episode 12

Evolving Role of Genomic Testing in RCC

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Kidney cancer is not a single disease, but rather is made up of several different types of cancer, including, for example, clear cell renal cell carcinoma (RCC), type 1 and type 2 papillary RCC, chromophobe RCC, and oncocytoma, notes Robert Figlin, MD. The role of genomic testing in kidney cancer is evolving, and Figlin questions whether molecular testing is useful in RCC to help identify actionable mutations and guide treatment selection.

Nizar M. Tannir, MD, uses genomic mutational analysis in specific scenarios. For example, Tannir recommends genomic testing for patients with refractory disease after several lines of therapy. Tannir describes a patient he recently treated, following the administration of all currently available targeted agents and still has good performance status. In this situation, genomic analysis of the patient’s tumor revealed an Erb mutation, providing the opportunity for enrollment in a clinical trial of a novel ErbB2 inhibitor.

Another clinical scenario in which genomic testing is useful, according to Tannir, is in difficult-to-diagnose patients, to elucidate whether the patient has either clear-cell histology, a VHL mutation, papillary RCC with chromosome 7 alteration, or the c-MET mutation. Tannir also uses genomic testing to evaluate patients with type 1 papillary RCC for the c-MET mutation, to identify appropriate patients for c-MET inhibitor trials.

Genomic testing may reveal many different abnormalities; however, Brian Rini, MD, comments that not all of these abnormalities may be driver mutations. Rini also notes that drugs are available for only a few mutations, and that the results of genomic testing are not actionable if there are no drugs that target the mutations identified.

Daniel J. George, MD, remarks that there are many loss of function mutations involved in kidney cancer; for example, 2, 3, or 4 tumor suppressor genes may be knocked out. However, few activating mutations have been identified to date. Although certain targets, such as ErbB2, PI3 kinase, and mTOR, have been identified, these mutations are seen in a minority of patients, and there remains a need to identify additional targets. George comments that further understanding of the biology of tumor suppressor genes is needed in order to build upon existing targeted approaches.