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Updated: Jul 1, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Targeted therapy for advanced renal cell cancer: cytokines and beyond
George S Papaetis1, Lena M Karapanagiotou, Hardev Pandha
1Oncology Unit, 3rd Department of Medicine, Athens School of Medicine, Athens, Greece.
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.
Insights
Targeted therapies offer new hope for advanced renal cell cancer (RCC) by inhibiting specific molecular pathways. While promising, these treatments present novel toxicities, necessitating further research into optimal use and combinations.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Cytokines have been the standard treatment for advanced renal cell cancer (RCC) for two decades, but exhibit low response rates and significant toxicity.
- Advances in understanding the VHL-HIF pathway have led to the development of novel targeted agents for RCC.
- Targeted therapies aim to inhibit specific molecular events driving cancer progression, potentially offering improved safety and efficacy.
Purpose of the Study:
- To review existing targeted therapies for advanced renal cell cancer (RCC).
- To present recent clinical data on targeted agents in RCC treatment.
- To discuss future perspectives and potential roles for IL-2 in combination therapy.
Main Methods:
- Comprehensive literature review of targeted therapies for RCC.
- Analysis of clinical trial data for novel RCC agents.
- Discussion of current research on administration regimens and combination therapies.
Main Results:
- Novel targeted agents show promise in stabilizing advanced RCC, with some achieving clinical licensure.
- Despite high specificity, new and unanticipated toxicities have emerged with targeted therapies.
- Optimal administration and synergistic combinations of targeted agents are under active investigation.
Conclusions:
- Targeted therapies represent a significant advancement in advanced RCC treatment, offering an alternative to traditional cytokine therapy.
- While effective, careful management of novel toxicities associated with targeted agents is crucial.
- Further research is needed to optimize the use of targeted therapies, including combination strategies and the potential role of IL-2 in specific patient subgroups.
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