p53 in Head and Neck Cancer

Chapter
Part of the Current Cancer Research book series (CUCR)

Abstract

Alteration of the TP53 tumor suppressor gene is a central event in the development of human malignancy. The majority of squamous cell carcinomas of the head and neck (HNC) have undergone this molecular disruption either by point mutation of TP53 or through disruption of p53 protein function as a consequence of oncogenic human papillomavirus (HPV) infection. p53 interactions with partner proteins control key cellular pathways that affect apoptosis, the cell cycle, and proliferation, particularly in response to stress. Early research demonstrated mutation in the coding region of TP53 in more than half of all HNC tumors. However, the anticipated value of TP53 alteration for clinical management of HNC has not materialized. This is due, in part, to the complexity of TP53 alterations, which occur at numerous loci within the gene and produce highly variable results with regard to protein function, as well as to the highly integrated position of p53 within densely connected cellular pathways that induce pleiotropic effects. Furthermore, as a tumor suppressor, p53 is not immediately accessible as a therapeutic target, since the restoration of protein activity is more difficult to achieve than the blockage of activity of a gain-of-function event. However, interest in TP53 alteration in HNC has undergone a minor renaissance with the observation that some mutations which disrupt the DNA-binding function of p53 are associated with more aggressive cancer phenotype than are mutations that are nondisruptive. Identification and targeting of this class of TP53 mutation may, hence, have clinical importance in the disease management of HNC. We summarize current relevant issues in TP53 biology.

Keywords

TP53 Disruptive mutation Detection Prognosis Human papillomavirus (HPV) Tumor suppressor gene Head and neck cancer Chemoresistance Targeted therapy 

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Otolaryngology, Asan Medical CenterCollege of Medicine, University of UlsanSeoulRepublic of Korea
  2. 2.Department of Otolaryngology-Head and Neck SurgeryJohns Hopkins University School of MedicineBaltimoreUSA

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