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The Role of Hepatocyte Growth Factor Pathway Signaling in Renal Cell Carcinoma

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Renal Cell Carcinoma

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Abstract

The urgent need for effective therapies for patients with advanced renal cell carcinoma (RCC), fewer than 20 % of whom will survive more than 2 years, has led to the identification of critical genetic determinants and associated molecular pathways contributing to RCC oncogenesis, progression, and spread. Among the signaling pathways dysregulated in RCC is that of hepatocyte growth factor (HGF), which through the cell surface receptor tyrosine kinase, Met, stimulates proliferation, motility, and morphogenesis. Germ line missense mutations in the tyrosine kinase domain Met are associated with hereditary papillary renal carcinoma (HPRC), while somatic mutations and frequent trisomy of chromosome 7 implicate pathway involvement in sporadic papillary type 1 RCC. In addition, loss of the VHL tumor suppressor gene results in the derepression of an embryonic HGF-driven phenotype likely to contribute to tumor invasiveness and metastasis in clear cell RCC. Our knowledge of HGF/Met signaling has enabled rapid progress in characterizing its contributions to RCC and in laying the framework for the development of novel anticancer therapeutics. A better understanding of how HGF/Met signaling is integrated with other oncogenic pathways in RCC should aid the development of combinatorial treatment strategies, and help predict potential adverse effects of long-term pathway blockade.

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Authors and Affiliations

  1. Urologic Oncology Branch, CCR, NCI, National Institutes of Health, Bethesda, MD, USA

    Fabiola Cecchi Ph.D., Young H. Lee Ph.D., Benedetta Peruzzi Ph.D. & Jean-Baptiste Lattouf M.D.

  2. DAI Diagnostica di Laboratorio – SOD Laboratorio Generale, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla, 3, Firenze, 50134, Italia

    Benedetta Peruzzi Ph.D.

  3. Department of Surgery, Hospital Center of the University of Montreal, 1058 Saint-Denis, Montreal, QC, Canada, H2X3J4

    Jean-Baptiste Lattouf M.D.

  4. Urologic Oncology Branch, CCR, NCI, National Institutes of Health, Bldg 10 CRC Rm 2-3852, 10 Center Drive MSC 1107, Bethesda, MD, 20892-1107, USA

    Donald P. Bottaro Ph.D.

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  1. Fabiola Cecchi Ph.D.
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  2. Young H. Lee Ph.D.
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  3. Benedetta Peruzzi Ph.D.
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  4. Jean-Baptiste Lattouf M.D.
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  5. Donald P. Bottaro Ph.D.
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Correspondence to Donald P. Bottaro Ph.D. .

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  1. Taussig Cancer Center, Cleveland Clinic, Pepper Pike, Ohio, USA

    Ronald M. Bukowski

  2. Division of Hematology Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA

    Robert A. Figlin

  3. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Robert J. Motzer

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Cecchi, F., Lee, Y.H., Peruzzi, B., Lattouf, JB., Bottaro, D.P. (2015). The Role of Hepatocyte Growth Factor Pathway Signaling in Renal Cell Carcinoma. In: Bukowski, R., Figlin, R., Motzer, R. (eds) Renal Cell Carcinoma. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1622-1_15

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