Abstract
Cytotoxic approaches to killing tumor cells, such as chemotherapeutic agents, γ-irradiation, suicide genes or immunotherapy, have been shown to induce cell death through apoptosis. The intrinsic apoptotic pathway is activated following treatment with cytotoxic drugs, and these reactions ultimately lead to the activation of caspases, which promote cell death in tumor cells. In addition, activation of the extrinsic apoptotic pathway with death-inducing ligands leads to an increased sensitivity of tumor cells toward cytotoxic stimuli, illustrating the interplay between the two cell death pathways. In contrast, tumor resistance to cytotoxic stimuli may be due to defects in apoptotic signaling. As a result of their importance in killing cancer cells, a number of apoptotic molecules are implicated in cancer therapy. The knowledge gleaned from basic research into apoptotic pathways from cell biological, structural, biochemical, and biophysical approaches can be used in strategies to develop novel compounds that eradicate tumor cells. In addition to current drug targets, research into molecules that activate procaspase – 3 directly may show the direct activation of the executioner caspase to be a powerful therapeutic strategy in the treatment of many cancers.
Keywords: Caspase, apoptosis, programmed cell death, protease, zymogen, dimerization, active site formation, human disease, cancer treatment, dimer interface
Current Cancer Drug Targets
Title: Targeting Cell Death in Tumors by Activating Caspases
Volume: 8 Issue: 2
Author(s): A. Clay Clark and Sarah H. MacKenzie
Affiliation:
Keywords: Caspase, apoptosis, programmed cell death, protease, zymogen, dimerization, active site formation, human disease, cancer treatment, dimer interface
Abstract: Cytotoxic approaches to killing tumor cells, such as chemotherapeutic agents, γ-irradiation, suicide genes or immunotherapy, have been shown to induce cell death through apoptosis. The intrinsic apoptotic pathway is activated following treatment with cytotoxic drugs, and these reactions ultimately lead to the activation of caspases, which promote cell death in tumor cells. In addition, activation of the extrinsic apoptotic pathway with death-inducing ligands leads to an increased sensitivity of tumor cells toward cytotoxic stimuli, illustrating the interplay between the two cell death pathways. In contrast, tumor resistance to cytotoxic stimuli may be due to defects in apoptotic signaling. As a result of their importance in killing cancer cells, a number of apoptotic molecules are implicated in cancer therapy. The knowledge gleaned from basic research into apoptotic pathways from cell biological, structural, biochemical, and biophysical approaches can be used in strategies to develop novel compounds that eradicate tumor cells. In addition to current drug targets, research into molecules that activate procaspase – 3 directly may show the direct activation of the executioner caspase to be a powerful therapeutic strategy in the treatment of many cancers.
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Cite this article as:
Clark Clay A. and MacKenzie H. Sarah, Targeting Cell Death in Tumors by Activating Caspases, Current Cancer Drug Targets 2008; 8 (2) . https://dx.doi.org/10.2174/156800908783769391
DOI https://dx.doi.org/10.2174/156800908783769391 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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