Abstract
For the past 20 years cytokines have been the mainstay of treatment for advanced renal cell cancer (RCC), despite low response rates achieved and the high toxicity profile observed. The recent advances in molecular biology and the greater understanding of the von Hippel-Lindau (VHL) hypoxia-inducible factor (HIF)-hypoxia-induced gene pathway have paved the way for a plethora of novel agents that selectively inhibit key molecular events which allow the malignant process to continue. The high specificity of targeted agents should allow sparing of healthy cells thereby making them less toxic and well tolerated. However, new and unanticipated toxicities have been described with virtually all new agents, some of which may even be of a similar magnitude to cytokine therapy. Although several agents have demonstrated promising results in clinical trials, especially in terms of disease stabilization, and achieved clinical licences, issues of optimal administration regimens as well as the possible synergy when combined together are currently being explored. In this new era, IL-2 may still have a relevant role in selected subgroups of patients as well in combination with novel agents. Our review describes thoroughly the existing targeted therapies for RCC, presenting the recent clinical data and discussing the perspectives.
Keywords: Endothelium, cytokines, VEGF, TGF-a, m-TOR, targeted therapy, angiogenesis
Current Pharmaceutical Design
Title: Targeted Therapy for Advanced Renal Cell Cancer: Cytokines and Beyond
Volume: 14 Issue: 22
Author(s): George S. Papaetis, Lena M. Karapanagiotou, Hardev Pandha and Kostas N. Syrigos
Affiliation:
Keywords: Endothelium, cytokines, VEGF, TGF-a, m-TOR, targeted therapy, angiogenesis
Abstract: For the past 20 years cytokines have been the mainstay of treatment for advanced renal cell cancer (RCC), despite low response rates achieved and the high toxicity profile observed. The recent advances in molecular biology and the greater understanding of the von Hippel-Lindau (VHL) hypoxia-inducible factor (HIF)-hypoxia-induced gene pathway have paved the way for a plethora of novel agents that selectively inhibit key molecular events which allow the malignant process to continue. The high specificity of targeted agents should allow sparing of healthy cells thereby making them less toxic and well tolerated. However, new and unanticipated toxicities have been described with virtually all new agents, some of which may even be of a similar magnitude to cytokine therapy. Although several agents have demonstrated promising results in clinical trials, especially in terms of disease stabilization, and achieved clinical licences, issues of optimal administration regimens as well as the possible synergy when combined together are currently being explored. In this new era, IL-2 may still have a relevant role in selected subgroups of patients as well in combination with novel agents. Our review describes thoroughly the existing targeted therapies for RCC, presenting the recent clinical data and discussing the perspectives.
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Cite this article as:
Papaetis S. George, Karapanagiotou M. Lena, Pandha Hardev and Syrigos N. Kostas, Targeted Therapy for Advanced Renal Cell Cancer: Cytokines and Beyond, Current Pharmaceutical Design 2008; 14 (22) . https://dx.doi.org/10.2174/138161208785740153
DOI https://dx.doi.org/10.2174/138161208785740153 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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