EGFR-PI3K-AKT-mTOR signaling in head and neck squamous cell carcinomas: attractive targets for molecular-oriented therapy.
BACKGROUND
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.


METHODS
Books, journals, databases and websites have been searched to provide a current review on the subject.


RESULTS
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.


CONCLUSIONS
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.
National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Head and Neck Surgery Branch, Bethesda, MD 20892, USA.
Christian
C
Freudlsperger
Jeffrey R
JR
Burnett
Jay A
JA
Friedman
Vishnu R
VR
Kannabiran
Zhong
Z
Chen
Carter
C
Van Waes
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D066246:ErbB Receptors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human