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Review
. 2011 Feb 1;104(3):399-406.
doi: 10.1038/sj.bjc.6606084.

Challenges and opportunities for converting renal cell carcinoma into a chronic disease with targeted therapies

M E Gore  1 , J M G Larkin
Affiliations
Review

Challenges and opportunities for converting renal cell carcinoma into a chronic disease with targeted therapies

M E Gore et al. Br J Cancer. .

Abstract

Optimum efficacy is the primary goal for any cancer therapy, and entails controlling tumour growth and prolonging survival as far as possible. The prognosis for patients with metastatic renal cell carcinoma (mRCC) has greatly improved with the introduction of targeted therapies. This review examines the development and efficacy of targeted agents for the management of mRCC, the challenges offered by their rapid emergence, and discusses how mRCC treatment may evolve in the future. Improvements in progression-free survival and overall survival rates, observed with targeted agents, indicate that it may now be possible to change mRCC from a rapidly fatal and largely untreatable condition into a chronic disease. The major challenges to further advances in targeted therapy for mRCC include overcoming drug resistance, identifying the most effective sequence or combination of targeted agents, optimising clinical trial design and managing the cost of treatment.

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Conflict of interest statement

Martin Gore has received honoraria from, and served on, the Speakers Bureau and Advisory Boards of Pfizer, Bayer, Wyeth, Roche and GSK. James Larkin has received honoraria from, and served on, the advisory boards of Pfizer, Bayer, GSK, AVEO and Novartis.

Figures

Figure 1
Figure 1
Resistance to targeted agents may occur through target bypass mechanisms. A targeted agent (denoted by X in the figure) may effectively inhibit the signalling cascade of one or more pathway (denoted by the light grey square and circle in the figure). However, the presence of a ‘bypass’ mechanism may allow this inhibition to be circumvented by signalling along an unknown or unrelated pathway (denoted by the light grey triangle in the figure), resulting in resistance to the targeted therapy.
Figure 2
Figure 2
Most common and side effects of interest reported with the six licensed targeted agents for mRCC.
Figure 3
Figure 3
Treatment strategies with targeted agents involve a sequential or a combinatorial approach; single-agent sequential therapy may cause tumour shrinkage but may also slow disease progression and, therefore, turn mRCC into a chronic disease.
See this image and copyright information in PMC

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