PMID- 21110697
OWN - NLM
STAT- MEDLINE
DCOM- 20110316
LR  - 20220318
IS  - 1744-7631 (Electronic)
IS  - 1472-8222 (Print)
IS  - 1472-8222 (Linking)
VI  - 15
IP  - 1
DP  - 2011 Jan
TI  - EGFR-PI3K-AKT-mTOR signaling in head and neck squamous cell carcinomas: 
      attractive targets for molecular-oriented therapy.
PG  - 63-74
LID - 10.1517/14728222.2011.541440 [doi]
AB  - IMPORTANCE OF THE FIELD: Recent advances in the understanding of the oncogenesis 
      of head and neck squamous cell carcinomas (HNSCC) have revealed multiple 
      dysregulated signaling pathways. One frequently altered axis is the 
      EGFR-PI3K-Akt-mTOR pathway. This pathway plays a central role in numerous 
      cellular processes including metabolism, cell growth, apoptosis, survival and 
      differentiation, which ultimately contributes to HNSCC progression. AREAS COVERED 
      IN THIS REVIEW: Books, journals, databases and websites have been searched to 
      provide a current review on the subject. WHAT THE READER WILL GAIN: This article 
      reviews the current understanding of EGFR-PI3K-Akt-mTOR signaling in HNSCC, 
      including the impact of both genetic and epigenetic alterations. This review 
      further highlights the potential of targeting this signaling cascade as a 
      promising therapeutic approach in the treatment of HNSCC. TAKE HOME MESSAGE: 
      Genetic alterations of several nodes within this pathway, including both genetic 
      and epigenetic changes, leading to either oncogene activation or inactivation of 
      tumor suppressors have frequently been implicated in HNSCC. Consequently, drugs 
      that target the central nodes of this pathway have become attractive for 
      molecular oriented cancer therapies. Numerous preclinical and clinical studies 
      are being performed in HNSCC; however, more studies are still needed to better 
      understand the biology of this pathway.
FAU - Freudlsperger, Christian
AU  - Freudlsperger C
AD  - National Institute on Deafness and Other Communication Disorders, National 
      Institutes of Health, Head and Neck Surgery Branch, Bethesda, MD 20892, USA.
FAU - Burnett, Jeffrey R
AU  - Burnett JR
FAU - Friedman, Jay A
AU  - Friedman JA
FAU - Kannabiran, Vishnu R
AU  - Kannabiran VR
FAU - Chen, Zhong
AU  - Chen Z
FAU - Van Waes, Carter
AU  - Van Waes C
LA  - eng
GR  - Z01 DC000073-01/ImNIH/Intramural NIH HHS/United States
GR  - ZIA DC000073/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20101126
PL  - England
TA  - Expert Opin Ther Targets
JT  - Expert opinion on therapeutic targets
JID - 101127833
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Carcinoma, Squamous Cell/*drug therapy/genetics/physiopathology
MH  - Drug Delivery Systems
MH  - ErbB Receptors/genetics/metabolism
MH  - Head and Neck Neoplasms/*drug therapy/genetics/physiopathology
MH  - Humans
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
PMC - PMC3399735
MID - NIHMS391465
COIS- Declaration of interest Gefitinib (Astra Zeneca) and PI3K-mTOR inhibitors 
      (Pfizer) have been provided for research and clinical trials through material 
      transfer and clinical trials agreements between these companies and the National 
      Cancer Institute or National Institute on Deafness and Other Communication 
      Disorders. Dr. Van Waes and the other authors declare no financial conflict of 
      interest and have received no payment in preparation of this manuscript.
EDAT- 2010/11/30 06:00
MHDA- 2011/03/17 06:00
PMCR- 2012/07/18
CRDT- 2010/11/30 06:00
PHST- 2010/11/30 06:00 [entrez]
PHST- 2010/11/30 06:00 [pubmed]
PHST- 2011/03/17 06:00 [medline]
PHST- 2012/07/18 00:00 [pmc-release]
AID - 10.1517/14728222.2011.541440 [doi]
PST - ppublish
SO  - Expert Opin Ther Targets. 2011 Jan;15(1):63-74. doi: 
      10.1517/14728222.2011.541440. Epub 2010 Nov 26.