Death receptors: Targets for cancer therapy

Apoptosis is the cell's intrinsic program to death, which plays an important role in physiologic growth control and homeostasis. Apoptosis can be triggered by death receptors (DRs), without any adverse effects. DRs are the members of tumor necrosis factor (TNF) receptor superfamily, known to be...

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Bibliographic Details
Published in:Experimental cell research 2010-04, Vol.316 (6), p.887-899
Main Authors: Mahmood, Zafar, Shukla, Yogeshwer
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Animals
Antineoplastic Agents - therapeutic use
APOPTOSIS
Apoptosis - physiology
Cancer
Cellular biology
CHEMOTHERAPY
Clinical Trials as Topic
DEATH
Death receptors
Ectodysplasin A receptor
Genetics
GROWTH FACTORS
HOMEOSTASIS
Humans
LIGANDS
Medical research
NEOPLASMS
Neoplasms - therapy
Nerve growth factor receptor
RADIOTHERAPY
RECEPTORS
Receptors, Death Domain - genetics
Receptors, Death Domain - metabolism
REVIEWS
SENSITIVITY
Signal Transduction - physiology
TNF-related apoptosis-inducing ligand
TOXICITY
Tumor necrosis factor
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Summary:Apoptosis is the cell's intrinsic program to death, which plays an important role in physiologic growth control and homeostasis. Apoptosis can be triggered by death receptors (DRs), without any adverse effects. DRs are the members of tumor necrosis factor (TNF) receptor superfamily, known to be involved in apoptosis signaling, independent of p53 tumor-supressor gene. Selective triggering of DR-mediated apoptosis in cancer cells is a novel approach in cancer therapy. So far, the best characterized DRs are CD95 (Fas/Apo1), TNF-related apoptosis-inducing ligand receptor (TRAILR) and tumor necrosis factor receptor (TNFR). Among these, TRAILR is emerging as most promising agent for cancer therapy, because it induces apoptosis in a variety of tumor and transformed cells without any toxicity to normal cells. TRAIL treatment in combination with chemotherapy or radiotherapy enhances TRAIL sensitivity or reverses TRAIL resistance by regulating downstream effectors. This review covers the current knowledge about the DRs, summarizes main signaling in DRs and also summarizes the preclinical approaches of these DRs in cancer therapy.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2009.12.011