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Renal Cell Carcinoma pp 335–346Cite as

Smac/DIABLO: A Proapoptotic Molecular Target in Renal Cell Cancer

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Abstract

Renal cell carcinoma (RCC) accounts for about 2% of all cancer cases worldwide. Metastatic disease is often present at time of diagnosis of RCC, and its poor prognosis is determined by its poor response to chemotherapy and radiotherapy. Immunotherapy including interleukin-2 and interferon-α is relatively effective against metastatic RCC; however, the response rate is 15–20%. Chemotherapy, immunotherapy and radiotherapy have been shown to mediate their cytotoxic and antitumor effects by inducing cell death by apoptosis. The poor response of RCC to conventional therapies may be due in large part to the development of resistance to cell death by apoptosis through the modification of apoptosis regulatory gene products. Such genes and their products may also have important utility as diagnostic/ prognostic markers and therapeutic targets in this disease. However, few genes of this nature have been found to date in RCC.

This chapter introduces second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pl (Smac/DIABLO), a gene product of significant prognostic and therapeutic significance in RCC. Smac/DIABLO was recently identified as a protein that is released from mitochondria in response to apoptotic stimuli and promotes apoptosis by antagonizing inhibitor of apoptosis proteins. Smac/DIABLO is a new biomarker for RCC. The level of expression of Smac/DIABLO and its biological activity determine in large part the pathogenesis and fate of RCC and its response to antitumor cytotoxic agents, including chemotherapy, immunotherapy, etc. In addition, Smac/DIABLO offers a promising target for therapy by agents that regulate its expression and stabilization. Such agents, when used in combination with subtoxic doses of chemotherapy and/or immuno-therapy, may be very effective in killing the resistant RCC cells and improve survival. Thus, the level of expression of Smac/DIABLO in RCC has implications in the pathogenesis, diagnosis, and the development of new treatment modalities.

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Authors and Affiliations

  1. Department of Urology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Yoichi Mizutani

  2. Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Akihiro Kawauchi & Tsuneharu Miki

  3. Department of Microbiology, Immunology, and Molecular Genetics, University of California at Los Angeles, Los Angeles, CA

    Benjamin Bonavida

Authors
  1. Yoichi Mizutani
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  2. Akihiro Kawauchi
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  3. Benjamin Bonavida
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  4. Tsuneharu Miki
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Corresponding author

Correspondence to Yoichi Mizutani .

Editor information

Editors and Affiliations

  1. Cleveland Clinic Foundation, Cleveland Clinic Taussig Cancer Center and CCF Lerner College of Medicine of CWRU, Cleveland, OH

    Ronald M. Bukowski

  2. Division of Medical Oncology & Experimental Therapeutics, City of Hope National Medical, Center/Beckman Research Institute, Duarte, CA

    Robert A. Figlin

  3. Memorial-Sloan Kettering Cancer Center, New York, NY

    Robert J. Motzer

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Mizutani, Y., Kawauchi, A., Bonavida, B., Miki, T. (2009). Smac/DIABLO: A Proapoptotic Molecular Target in Renal Cell Cancer. In: Bukowski, R.M., Figlin, R.A., Motzer, R.J. (eds) Renal Cell Carcinoma. Humana Press. https://doi.org/10.1007/978-1-59745-332-5_19

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  • DOI: https://doi.org/10.1007/978-1-59745-332-5_19

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-737-2

  • Online ISBN: 978-1-59745-332-5

  • eBook Packages: MedicineMedicine (R0)

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