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Apoptosis and Cancer: Mutations within Caspase Genes
  1. Saeid Ghavami (ghavami{at}cc.umanitoba.ca)
  1. Departments of Physiology, Univ. Manitoba, Canada
    1. Mohammad Hashemi (hashemim{at}zdmu.ac.ir)
    1. Department of Clinical Biochemistry, and Cellular Molecular Research Centre, Zahedan University, Iran, Islamic Republic of
      1. Sudharsana R Ande (ande{at}cc.umanitoba.ca)
      1. MICB, Cancer Care Manitoba, Canada
        1. Behzad Yeganeh
        1. Department of Biochemistry & Medical Genetics, Faculty of Medicine, Univ. Manitoba, Canada
          1. Wenyan Xiao (wyjessie{at}hotmail.com)
          1. MICB, Cancer Care Manitoba, Canada
            1. Mehdi Eshraghi (wyjessie{at}hotmail.com)
            1. Department of Biochemistry & Medical Genetics, Faculty of Medicine, Univ. Manitoba, Canada
              1. Christine J Bus (christinebus{at}aol.com)
              1. Interfaculty Institute of Biochemistry, University of Tübingen, Germany
                1. Kamran Kadkhoda (kadkhodk{at}cc.umanitoba.ca)
                1. Diagnostic Services of Manitoba, Canada
                  1. Emilia Wiechec (emilia{at}humgen.au.dk)
                  1. Department of Human Genetics, Univ. Aarhus, Denmark
                    1. Andrew J Halayko (ahalayk{at}cc.umanitoba.ca)
                    1. Departments of Physiology, Univ. Manitoba, Canada
                      1. Marek Los (marek.los{at}ifib.uni-tuebingen.de)
                      1. Interfaculty Institute of Biochemistry, University of Tübingen, Germany

                        Abstract

                        The inactivation of programmed cell death has profound effects not only on the development but also on the overall integrity of multicellular organisms. Beside developmental abnormalities, it may lead to tumorigenesis, autoimmunity, and other serious health problems. Deregulated apoptosis may also be the leading cause of cancer therapy chemoresistance. Caspase family of cysteinyl-proteases plays the key role in the initiation and execution of programmed cell death. This review gives an overview of the role of caspases, their natural modulators like IAPs, FLIPs, and Smac/Diablo in apoptosis and upon inactivation, also in cancer development. Besides describing the basic mechanisms governing programmed cell death, large part of this review is dedicated to previous studies that were focused on screening tumors for mutations within caspase genes as well as their regulators. Last part of this review discusses several emerging treatments that involve modulation of caspases and their regulators. Thus, we also highlight caspase cascade-modulating experimental anticancer drugs like cFLIP-antagonist CDDO-Me; cIAP1 antagonists OSU-03012 and ME-BS; and XIAP small molecule antagonists 1396-11, 1396-12, 1396-28, triptolide, AEG35156, survivin/Hsp90 antagonist shephedrin, and some of the direct activators of procaspase-3.

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