PMID- 23813857
OWN - NLM
STAT- MEDLINE
DCOM- 20140317
LR  - 20130813
IS  - 1872-8081 (Electronic)
IS  - 0951-6433 (Linking)
VI  - 39
IP  - 4
DP  - 2013 Jul-Aug
TI  - The TRAIL of oncogenes to apoptosis.
PG  - 343-54
LID - 10.1002/biof.1112 [doi]
AB  - Despite the significant advances in clinical research, surgical resection, 
      radiotherapy and chemotherapy are still used as the primary method for cancer 
      treatment. As compared to conventional therapies that often induce systemic 
      toxicity and eventually contribute to tumor resistance, the TNF-related 
      apoptosis-inducing ligand (TRAIL) is a promising anticancer agent that 
      selectively triggers apoptosis in various cancer cells by interacting with its 
      proapoptotic receptors DR4 and KILLER/DR5, while sparing the normal surrounding 
      tissue. The intensive studies of TRAIL signaling pathways over the past decade 
      have provided clues for understanding the molecular mechanisms of TRAIL-induced 
      apoptosis in carcinogenesis and identified an array of therapeutic responses 
      elicited by TRAIL and its receptor agonists. Analysis of its activity at the 
      molecular level has shown that TRAIL improves survival either as monotherapies or 
      combinatorial therapies with other mediators of apoptosis or anticancer 
      chemotherapy. Combinatorial treatments amplify the activities of anticancer 
      agents and widen the therapeutic window by overcoming tumor resistance to 
      apoptosis and driving cancer cells to self-destruction. Although TRAIL 
      sensitivity varies widely depending on the cell type, nontransformed cells are 
      largely resistant to death mediated by TRAIL Death Receptors (DRs). Genetic 
      alterations in cancer can contribute in tumor progression and often play an 
      important role in evasion of apoptosis by tumor cells. Remarkably, RAS, MYC and 
      HER2 oncogenes have been shown to sensitise tumor cells to TRAIL induced cell 
      death. Here, we summarise the cross-talk of oncogenic and apoptotic pathways and 
      how they can be exploited toward efficient combinatorial therapeutic protocols.
CI  - Copyright (c) 2013 International Union of Biochemistry and Molecular Biology, Inc.
FAU - Oikonomou, Eftychia
AU  - Oikonomou E
AD  - Laboratory of Signal Mediated Gene Expression, Institute of Biology, Medicinal 
      Chemistry and Biotechnology, National Hellenic Research Foundation, 48, Vasileos 
      Konstantinou Ave., 11635, Athens, Greece.
FAU - Pintzas, Alexander
AU  - Pintzas A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20130629
PL  - Netherlands
TA  - Biofactors
JT  - BioFactors (Oxford, England)
JID - 8807441
RN  - 0 (Antineoplastic Agents)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology/therapeutic use
MH  - *Apoptosis
MH  - Drug Resistance, Neoplasm
MH  - Humans
MH  - MAP Kinase Signaling System
MH  - Molecular Targeted Therapy
MH  - Neoplasms/*drug therapy/genetics/metabolism
MH  - *Oncogenes
MH  - TNF-Related Apoptosis-Inducing Ligand/*pharmacology/physiology/therapeutic use
OTO - NOTNLM
OT  - RAS oncogenes
OT  - TRAIL
OT  - apoptosis
OT  - cancer therapy
OT  - kinase inhibitors
EDAT- 2013/07/03 06:00
MHDA- 2014/03/19 06:00
CRDT- 2013/07/02 06:00
PHST- 2013/04/22 00:00 [received]
PHST- 2013/04/25 00:00 [accepted]
PHST- 2013/07/02 06:00 [entrez]
PHST- 2013/07/03 06:00 [pubmed]
PHST- 2014/03/19 06:00 [medline]
AID - 10.1002/biof.1112 [doi]
PST - ppublish
SO  - Biofactors. 2013 Jul-Aug;39(4):343-54. doi: 10.1002/biof.1112. Epub 2013 Jun 29.