The changing face of p53 in head and neck cancer.
p53 plays a sentinel role in the pathways that prevent development of cancer by inducing apoptosis, DNA repair and cell-cycle arrest in response to different types of cellular stress. The majority of head and neck tumours harbour mutations affecting the p53 gene, and those tumours that seemingly have wild-type p53 protein most probably lack a functional p53 response as a result of mutations affecting other genes that function in the same pathways as p53. This report provides an up-to-date overview of what is known about how p53 exerts its effects. We also summarize what is known about the other p53 family members, p63 and p73, and show how they act together to influence the response to treatment. No other commonly occurring signature mutation has emerged for this tumour type, and this means that the p53 family has emerged as the frontrunner in terms of providing molecular targets that can provide new diagnostic, prognostic and therapeutic approaches.
Partridge
M
M
Kings College Hospital Maxillofacial Unit, Kings College London, Denmark Hill, London SE5 8RX, UK. oralsurgery@partridgekcl.co.uk <oralsurgery@partridgekcl.co.uk>
Costea
D E
DE
Huang
X
X
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology; D016158:Genes, p53 / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D015316:Genetic Therapy / Q000379:methods; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D010454:Peptide Termination Factors / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000235:genetics; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics
D000964:Antimetabolites, Antineoplastic; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010454:Peptide Termination Factors; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C087971:peptide-chain-release factor 3; D005472:Fluorouracil