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December 5, 2019

Progress Toward Precision Medicine in Frontline Treatment of Metastatic Renal Cell Carcinoma

Author Affiliations
  • 1Department of Urology, University of Texas Southwestern Medical Center, Dallas
  • 2Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
JAMA Oncol. 2020;6(1):25-26. doi:10.1001/jamaoncol.2019.4716

As molecular understanding of cancer biology evolves, precision medicine will play a growing role in guiding therapy. This is certainly evident in the case of metastatic renal cell carcinoma (mRCC), which is inherently a heterogeneous tumor type on both clinical and molecular levels. The treatment approach for mRCC has evolved considerably over the past couple of decades, since the original cytokine era of interleukin-2 and interferon-α. The targeted therapy era for mRCC, which dominated throughout most of the 2000s, was the first foray into precision medicine.1 It capitalized on pathways implicated in tumorigenesis and disease progression. Among the therapeutic classes introduced, angiogenic inhibitors emerged as the most promising agents and defined the new standard of care for treating mRCC. The efficacy of these agents highlights the unique biology underlying clear-cell renal cell carcinoma (ccRCC), the most common histologic subtype, in which von Hippel–Lindau gene (VHL) inactivation induces angiogenesis via the accumulation of hypoxia-inducible factors. Although encouraging, several patients with ccRCC have remained resistant to these therapies,2 requiring novel approaches to treatment.

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