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      Targeted therapies for renal cell carcinoma

      Author(s): , ,
      Publication date Created:
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      Journal: Nature Reviews Nephrology
      Publisher: Springer Nature

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          Abstract

          This Review provides an overview of the molecular determinants of renal cell carcinoma, how understanding the underlying mechanisms of disease has fuelled the development of targeted therapies, and tools to assess the value of these agents.

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          Most cited references69

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          The blockade of immune checkpoints in cancer immunotherapy.

          Drew M Pardoll (2012)
          Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
          Article 0 comments Cited 5647 times – based on 0 reviews     Review now
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            Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial.

            Toni K. Choueiri, Bernard Escudier, Thomas Powles … (2016)
            Cabozantinib is an oral inhibitor of tyrosine kinases including MET, VEGFR, and AXL. The randomised phase 3 METEOR trial compared the efficacy and safety of cabozantinib versus the mTOR inhibitor everolimus in patients with advanced renal cell carcinoma who progressed after previous VEGFR tyrosine-kinase inhibitor treatment. Here, we report the final overall survival results from this study based on an unplanned second interim analysis.
            Article 0 comments Cited 351 times – based on 0 reviews     Review now
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              Mutations of the VHL tumour suppressor gene in renal carcinoma.

              J R Gnarra, K Tory, Y. Weng … (1994)
              Multiple, bilateral renal carcinomas are a frequent occurrence in von Hippel-Lindau (VHL) disease. To elucidate the aetiological role of the VHL gene in human kidney tumorigenesis, localized and advanced tumours from 110 patients with sporadic renal carcinoma were analysed for VHL mutations and loss of heterozygosity (LOH). VHL mutations were identified in 57% of clear cell renal carcinomas analysed and LOH was observed in 98% of those samples. Moreover, VHL was mutated and lost in a renal tumour from a patient with familial renal carcinoma carrying the constitutional translocation, t(3;8)(p14;q24). The identification of VHL mutations in a majority of localized and advanced sporadic renal carcinomas and in a second form of hereditary renal carcinoma indicates that the VHL gene plays a critical part in the origin of this malignancy.
              Article 0 comments Cited 314 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Title: Nature Reviews Nephrology
                Abbreviated Title: Nat Rev Nephrol
                Publisher: Springer Nature
                ISSN (Print): 1759-5061
                ISSN (Electronic): 1759-507X
                Publication date Created: July 10 2017
                Publication date (Print): July 10 2017
                Volume:
                Issue:
                Article
                DOI: 10.1038/nrneph.2017.82
                PubMed ID: 28691713
                SO-VID: e089a67d-3ad3-4daf-b418-5e30d9210eeb
                Copyright © © 2017
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