Tumor biology and prognostic factors in renal cell carcinoma

Abstract

In the past 15 years, there has been an increased understanding of the tumor biology of renal cell carcinoma (RCC). The identification of vascular endothelial growth factor (VEGF), its related receptor (VEGFR), and the mammalian target of rapamycin as dysregulated signaling pathways in the development and progression of RCC has resulted in the rational development of pharmaceutical agents capable of specifically targeting key steps in these pathways. Clinical trials have demonstrated survival benefit with these agents, particularly in clear cell RCC patients. However, metastatic RCC will progress in all patients, resulting in a critical need to determine patient risk and optimize treatment. The goal of this article is to highlight the significant breakthroughs made in understanding the critical genetic alterations and signaling pathways underlying the pathogenesis of RCC. The discovery of prognostic factors and development of comprehensive nomograms to stratify patient risk and predictive biomarkers to facilitate individualized treatment selection and predict patient response to therapy also are reviewed.

Figure 1.

Important pathways involved in renal cell carcinoma biology and tumorigenesis [11]. Abbreviations: 4e-BP1, 4E binding protein 1; CAIX, carbonic anhydrase IX; EGF, epidermal growth factor; EGFR, EGF receptor; GLUT-1, glucose transporter 1; HIF, hypoxia-inducible factor; IGF, insulin-like growth factor; MAPK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; PDGF, platelet-derived growth factor; PI3K, phosphatidylinositol-3-kinase; PTEN, phosphatase and tensin homologue deleted on chromosome ten; TGF-α, transforming growth factor α; VEGF, vascular endothelial growth factor; VHL, von Hippel Lindau. Reprinted from Klatte T, Pantuck AJ. Molecular biology of renal cortical tumors. Urol Clin North Am 2008;35:573–580, copyright 2010, with permission from Elsevier.

Figure 2.

University of California Integrated Staging System [2]. Abbreviations: ECOG, Eastern Cooperative Oncology Group. Copyright © MedReviews®, LLC. Reprinted with permission of MedReviews®, LLC. Klatte T, Pantuck AJ, Kleid MD et al. Understanding the natural biology of kidney cancer: Implications for targeted cancer therapy. Rev Urol 2007;9: 47–56. Reviews in Urology is a copyrighted publication of MedReviews®, LLC. All rights reserved.

Figure 3.

Kaplan–Meier survival estimates (disease-specific survival) according to University of California Integrated Staging System risk groups [2]. Copyright © MedReviews®, LLC. Reprinted with permission of MedReviews®, LLC. Klatte T, Pantuck AJ, Kleid MD et al. Understanding the natural biology of kidney cancer: Implications for targeted cancer therapy. Rev Urol 2007;9: 47–56. Reviews in Urology is a copyrighted publication of MedReviews®, LLC. All rights reserved.