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Targeted therapies for renal cell carcinoma

Nature Reviews Nephrology volume 13, pages 496–511 (2017)Cite this article

Subjects

Key Points

  • Emerging treatments for renal cell carcinoma (RCC), including kinase inhibitors, checkpoint inhibitors, and combinations of these new agents, are improving outcomes for patients

  • A need for biomarkers of response to treatment and tools to personalize RCC care has emerged owing to the expanding number of available therapeutic options

  • Alternatives to needle biopsy, such as cell free DNA and circulating tumour cells might be needed to address the dynamic and heterogeneous nature of cancer to optimize treatment personalization

  • Perioperative systemic therapy is being actively studied as an adjunct to nephrectomy in the management of locally advanced RCC but remains investigational at this time

  • The rising cost of effective agents and the growing interest in combinatorial approaches require that, in addition to efficacy and toxicity, value is taken into account in formal frameworks

Abstract

The management of patients with metastatic renal cell carcinoma (RCC) has changed dramatically over the past few years. Nephrectomy remains an important intervention for localized RCC but systemic therapy is the mainstay of treatment for patients who relapse after surgery or who have metastatic RCC. Before 2005, medical therapies for RCC were limited to cytokine therapies, which are very toxic and benefit only a small percentage of patients. In 2017, therapeutic agents now include kinase and immune checkpoint inhibitors. Contemporary research with these agents is now focusing on combinatorial and perioperative therapy. The field is now faced with the evolving challenge of how to select the best therapy for each patient during their natural history of disease, which has created a strong interest in modern sequencing and molecular approaches to identify biomarkers to personalize treatments. New therapeutic agents and approaches are associated with different toxicities and financial burdens, which require consideration of value by measuring clinical benefit, toxicity, and the cost of each drug with an organized framework. In this Review, we discuss the mechanisms underlying RCC and how improved molecular understanding helped the development of therapies, as well as biomarkers of response to treatment. We also discuss the value of these agents and their impact on personalization of therapy and drug development for RCC.

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Figure 1: Targetable factors in the tumour-microenvironment interface in kidney cancer.
Figure 2: Factors that affect value-based cancer care.

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Authors and Affiliations

  1. Department of Pharmacy Services, Urologic Oncology Program & Translational Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, 90048, California, USA

    Edwin M. Posadas, Suwicha Limvorasak & Robert A. Figlin

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E.M.P. and S.L. researched data for the article and all authors discussed the article's content, wrote the text and reviewed or edited the article before submission.

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Posadas, E., Limvorasak, S. & Figlin, R. Targeted therapies for renal cell carcinoma. Nat Rev Nephrol 13, 496–511 (2017). https://doi.org/10.1038/nrneph.2017.82

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