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Cancer

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Supplement: Innovations and Challenges in Renal Cancer: Proceedings of the Third Cambridge Conference, Supplement to Cancer

15 May 2009

Volume 115, Issue S10

Pages i–x, 2247–2375

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  1. Supplement

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    2. Supplement
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      Innovations and challenges in renal cancer: Summary statement from the Third Cambridge Conference (pages 2247–2251)

      Michael B. Atkins, Ronald M. Bukowski, Bernard J. Escudier, Robert A. Figlin, Gary H. Hudes, William G. Kaelin Jr, W. Marston Linehan, David F. McDermott, James W. Mier, Ivan Pedrosa, Brian I. Rini, Sabina Signoretti, Jeffrey A. Sosman, Bin Tean Teh, Christopher G. Wood, Amado J. Zurita and Laura King

      Version of Record online: 28 APR 2009 | DOI: 10.1002/cncr.24229

      The Third Cambridge Conference on Innovations and Challenges in Renal Cancer was convened to discuss the current state of knowledge in the field, critique new data, stimulate communication among those involved in basic and clinical research, and offer recommendations for further study. Four main topics were discussed: genetics and molecular biology of renal cell cancer, staging and prognosis, systemic therapy, and correlative science and biomarkers in stage IV disease.

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      Hereditary kidney cancer : Unique Opportunity for Disease-based Therapy (pages 2252–2261)

      W. Marston Linehan, Peter A. Pinto, Gennady Bratslavsky, Elizabeth Pfaffenroth, Maria Merino, Cathy D. Vocke, Jorge R. Toro, Donald Bottaro, Len Neckers, Laura S. Schmidt and Ramaprasad Srinivasan

      Version of Record online: 28 APR 2009 | DOI: 10.1002/cncr.24230

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      The study of families with kidney cancer has led to the identification of the von Hippel-Lindau or VHL gene, the met proto-oncogene MET, the Birt-Hogg-Dube or BHD gene, and the fumarate hydratase gene. Understanding the pathways of these kidney cancer genes has provided the foundation for the development of targeted therapeutic approaches for the treatment of patients with kidney cancer.

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      Treatment of kidney cancer : Insights Provided by the VHL Tumor-Suppressor Protein (pages 2262–2272)

      William G. Kaelin Jr

      Version of Record online: 28 APR 2009 | DOI: 10.1002/cncr.24232

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      Germline inactivation of the VHL tumor suppressor gene is associated with an increased risk of clear cell carcinoma of the kidney in the context of von Hippel-Lindau (VHL) disease. The VHL protein has multiple functions that might be linked to tumor suppression, including targeting the hypoxia-inducible factor transcription factor for polyubiquitylation and proteasomal degradation.

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      Prognostic factors for survival in metastatic renal cell carcinoma : Update 2008 (pages 2273–2281)

      Ronald M. Bukowski

      Version of Record online: 28 APR 2009 | DOI: 10.1002/cncr.24226

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      A variety of clinical, pathologic, and molecular factors have been studied, but current models use predominantly easily obtained clinical factors. These approaches are reviewed, and current approaches to further refine and develop these techniques are reviewed.

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      Complexity of tumor vasculature in clear cell renal cell carcinoma (pages 2282–2289)

      Chao-Nan Qian, Dan Huang, Bill Wondergem and Bin Tean Teh

      Version of Record online: 28 APR 2009 | DOI: 10.1002/cncr.24238

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      Differential analysis of the tumor vasculature in clear cell renal cell carcinoma revealed complicated vasculature features correlating with prognosis in contrasting ways. The discrepancy in prognostic correlation between protein and messenger RNA levels of vascular endothelial growth factor was investigated.

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      Tissue biomarkers in renal cell carcinoma: Issues and solutions (pages 2290–2297)

      Arianna Di Napoli and Sabina Signoretti

      Version of Record online: 28 APR 2009 | DOI: 10.1002/cncr.24233

      The establishment of standardized operating procedures is necessary to maximize the accuracy of tissue-based biomarker assays. In this article, the authors discuss current issues in tissue-based translational research aimed at identifying clinically useful biomarkers for kidney cancer.

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      Immunotherapy of metastatic renal cell carcinoma (pages 2298–2305)

      David F. McDermott

      Version of Record online: 28 APR 2009 | DOI: 10.1002/cncr.24236

      In recent years, randomized trials have suggested that high-dose, intravenous bolus interleukin-2 (IL-2) is superior in terms of response rate and possibly response quality to regimens that involve either low-dose IL-2 and interferon‒α (IFN-α), intermediate- or low-dose IL-2 alone, or low-dose IFN-α alone in the treatment of renal cell carcinoma. More significantly, investigations associated with these trials suggest that the potential exists for identifying predictors of response (or resistance) and limiting IL-2 therapy to those most likely to benefit.

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      Vascular endothelial growth factor-targeted therapy in metastatic renal cell carcinoma (pages 2306–2312)

      Brian I. Rini

      Version of Record online: 28 APR 2009 | DOI: 10.1002/cncr.24227

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      Vascular endothelial growth factor (VEGF) is a potent proangiogenic protein that drives the fundamental biology of renal cell carcinoma (RCC) tumors. Approaches to inhibiting the action of VEGF through various mechanisms have demonstrated exceptional clinical effects in metastatic RCC.

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      Targeting mTOR in renal cell carcinoma (pages 2313–2320)

      Gary R. Hudes

      Version of Record online: 28 APR 2009 | DOI: 10.1002/cncr.24239

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      Inhibitors of the mammalian target of rapamycin (mTOR) are effective treatment for many patients with advanced renal cell carcinoma (RCC). Temsirolimus increases overall survival in patients with metastatic RCC and multiple risk factors for short survival. Everolimus increases progression-free survival in patients with metastatic RCC that has progressed after sunitinib, sorafenib, and other therapies. Newer clinical investigations that focus on the possibility of improving treatment outcomes involve combinations of an mTOR inhibitor with bevacizumab or sorafenib, agents active against RCC, but with different mechanisms of action. Possible mechanisms of resistance to mTOR inhibition have been identified, and may be reduced through combination of an mTOR inhibitor with other targeted agents.

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      Sequential therapy in renal cell carcinoma (pages 2321–2326)

      Bernard Escudier, Marine Gross Goupil, Christophe Massard and Karim Fizazi

      Version of Record online: 28 APR 2009 | DOI: 10.1002/cncr.24241

      Because of the recent approval of several drugs for the treatment of renal cell carcinoma, the use of sequential therapy has become standard. However, to the authors' knowledge, there is very little evidence that using all these drugs sequentially improves survival. By adding these drugs in an adequate order, one can expect an increase in overall progression-free survival of up to 27 months, which hopefully will result in a significant improvement in the overall survival of patients with renal cell carcinoma.

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      Treatment selection for patients with metastatic renal cell carcinoma (pages 2327–2333)

      Michael B. Atkins, Toni K. Choueiri, Daniel Cho, Meredith Regan and Sabina Signoretti

      Version of Record online: 28 APR 2009 | DOI: 10.1002/cncr.24231

      The availability of approved agents with distinct mechanisms of action (immunotherapy, vascular endothelial growth factor pathway, and mammalian target of rapamycin inhibitors) has encouraged investigations into identifying optimal treatment strategies for specific patients and specific tumor features. Recent data regarding clinical, tumor, and imaging features can provide some guidance in treatment selection, although more research is needed to identify and validate selection models and enable rational and optimal utilization of the currently available treatment options.

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      Magnetic resonance imaging as a biomarker in renal cell carcinoma (pages 2334–2345)

      Ivan Pedrosa, David C. Alsop and Neil M. Rofsky

      Version of Record online: 28 APR 2009 | DOI: 10.1002/cncr.24237

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      Magnetic resonance imaging (MRI) provides a noninvasive method for the identification of certain imaging features associated with specific histologic subtypes in renal cell carcinoma (RCC). Furthermore, assessment of tumor vascularity in RCC is feasible with contrast-enhanced and noncontrast MRI techniques, such as arterial spin labeling, and may serve as a method for monitoring the changes in tumor blood flow that accompany antiangiogenic therapy.

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      Circulating biomarkers for vascular endothelial growth factor inhibitors in renal cell carcinoma (pages 2346–2354)

      Amado J. Zurita, Eric Jonasch, Hua-Kang Wu, Hai T. Tran and John V. Heymach

      Version of Record online: 28 APR 2009 | DOI: 10.1002/cncr.24228

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      Recent studies have suggested that some of the biomarkers under investigation in clear cell renal cell carcinoma for vascular endothelial growth factor pathway inhibitors are promising, including circulating proangiogenic factors and receptors; markers of hypoxia and endothelial damage; and cellular populations in peripheral blood, such as circulating endothelial cells. Further preclinical and translational validation studies are still needed to determine their practical utility in the clinical setting.

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      Neoadjuvant (presurgical) therapy for renal cell carcinoma: A new treatment paradigm for locally advanced and metastatic disease (pages 2355–2360)

      Christopher G. Wood and Vitaly Margulis

      Version of Record online: 28 APR 2009 | DOI: 10.1002/cncr.24240

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      The authors reviewed their experience with neoadjuvant systemic therapy administered before cytoreductive surgery for metastatic, locally recurrent, or regionally advanced renal cell carcinoma. They found that neoadjuvant (presurgical) targeted therapy before cytoreductive surgery appears safe in the setting of metastatic renal cell carcinoma.

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      Novel therapeutics for metastatic renal cell carcinoma (pages 2361–2367)

      Thomas E. Hutson and Robert A. Figlin

      Version of Record online: 28 APR 2009 | DOI: 10.1002/cncr.24235

      Novel agents for the treatment of renal cell carcinoma are currently in clinical development, some of which target novel pathways not yet exploited as therapy for renal cell carcinoma. Recently reported and ongoing clinical trials will help further define the role of these agents as therapy for metastatic renal cell carcinoma.

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      Combination targeted therapy in advanced renal cell carcinoma (pages 2368–2375)

      Jeffrey Sosman and Igor Puzanov

      Version of Record online: 28 APR 2009 | DOI: 10.1002/cncr.24234

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      There are several newly approved antiangiogenic agents that are effective in patients with advanced renal cell cancer that clearly have improved the outcome for these patients. Because these agents are not curative, there is a significant opportunity to improve on them; combination therapy is 1 approach being pursued with early success but in the face of unexpected toxic effects at this time.

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