Strategies to overcome therapeutic resistance in renal cell carcinoma

• Published in: Urologic oncology 2017-03, Vol.35 (3), p.102-110
• Main Authors: Siska, Peter J., M.D, Beckermann, Kathryn E., M.D., Ph.D, Rathmell, W. Kimryn, M.D., Ph.D, Haake, Scott M., M.D
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Carcinoma, Renal Cell - immunology; Carcinoma, Renal Cell - mortality; Carcinoma, Renal Cell - pathology; Carcinoma, Renal Cell - therapy; Clinical Trials as Topic; Costimulatory and Inhibitory T-Cell Receptors - antagonists & inhibitors; Cytotoxicity, Immunologic - drug effects; Disease Progression; Disease-Free Survival; Drug Resistance, Neoplasm; Humans; Immunotherapy - methods; Kidney - blood supply; Kidney - pathology; Kidney Neoplasms - immunology; Kidney Neoplasms - mortality; Kidney Neoplasms - pathology; Kidney Neoplasms - therapy; Neoplasm Recurrence, Local - immunology; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - pathology; Neoplasm Recurrence, Local - therapy; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - pathology; Nephrectomy; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Receptors, Vascular Endothelial Growth Factor - metabolism; Signal Transduction - drug effects; TOR Serine-Threonine Kinases - metabolism; Urology
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2016.12.002

Abstract Background Renal cell cancer (RCC) is a prevalent and lethal disease. At time of diagnosis, most patients present with localized disease. For these patients, the standard of care includes nephrectomy with close monitoring thereafter. While many patients will be cured, 5-year recurrence rates range from 30% to 60%. Furthermore, nearly one-third of patients present with metastatic disease at time of diagnosis. Metastatic disease is rarely curable and typically lethal. Cytotoxic chemotherapy and radiation alone are incapable of controlling the disease. Extensive effort was expended in the development of cytokine therapies but response rates remain low. Newer agents targeting angiogenesis and mTOR signaling emerged in the 2000s and revolutionized patient care. While these agents improve progression free survival, the development of resistance is nearly universal. A new era of immunotherapy is now emerging, led by the checkpoint inhibitors. However, therapeutic resistance remains a complex issue that is likely to persist. Methods and Purpose In this review, we systematically evaluate preclinical research and clinical trials that address resistance to the primary RCC therapies, including anti-angiogenesis agents, mTOR inhibitors, and immunotherapies. As clear cell RCC is the most common adult kidney cancer and has been the focus of most studies, it will be the focus of this review.