Cutting-edge apoptosis-based therapeutics: a panacea for cancer?

Defects in programmed cell death or apoptosis are major hallmarks of cancer contributing to tumorigenesis, tumor progression, and therapy resistance. In the past decade, many of the pathways leading to apoptosis, as well as the molecular mechanisms blocking the death of tumor cells, have been elucid...

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Bibliographic Details
Published in:BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy biopharmaceuticals, and gene therapy, 2007-01, Vol.21 (5), p.273-297
Main Authors: Fischer, Ute, Janssen, Katja, Schulze-Osthoff, Klaus
Format: Article
Language:English
Subjects:
Animals
Anticarcinogenic Agents - chemistry
Anticarcinogenic Agents - pharmacology
Anticarcinogenic Agents - therapeutic use
Apoptosis - drug effects
Drug Design
Humans
Models, Biological
Neoplasms - drug therapy
Neoplasms - pathology
Technology, Pharmaceutical - methods
Technology, Pharmaceutical - trends
TNF-Related Apoptosis-Inducing Ligand - chemistry
TNF-Related Apoptosis-Inducing Ligand - pharmacology
TNF-Related Apoptosis-Inducing Ligand - therapeutic use
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Summary:Defects in programmed cell death or apoptosis are major hallmarks of cancer contributing to tumorigenesis, tumor progression, and therapy resistance. In the past decade, many of the pathways leading to apoptosis, as well as the molecular mechanisms blocking the death of tumor cells, have been elucidated. This detailed knowledge of the core apoptosis machinery is now being exploited for translation into novel cancer therapies in order to restore apoptosis induction in tumor cells. Strategies include activation of proapoptotic mediators such as death receptors, tumor protein p53, and second mitochondria-derived activator of caspases (SMAC)/DIABLO as well as inhibition of endogenous apoptosis inhibitors such as IAPs (inhibitor of apoptosis proteins) and BCL-2 (B-cell chronic lymphoid leukemia/lymphoma) proteins. Several approaches employing gene therapy and antisense strategies, recombinant biologics, or classic organic and combinatorial chemistry, have advanced into clinical trials or are already approved. This review looks at recent developments in apoptosis-based cancer therapies and highlights some very promising advances in drug design.
ISSN:1173-8804
DOI:10.2165/00063030-200721050-00001