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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
The changing face of p53 in head and neck cancer
M Partridge1, D E Costea, X Huang
1Kings College Hospital Maxillofacial Unit, Kings College London, Denmark Hill, London SE5 8RX, UK. oralsurgery@partridgekcl.co.uk <oralsurgery@partridgekcl.co.uk>
Abstract:
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.
Insights
Mutations in the p53 gene and its family members are common in head and neck cancers. Targeting the p53 family offers promising new strategies for cancer diagnosis, prognosis, and treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The p53 tumor suppressor protein is crucial for preventing cancer by initiating apoptosis, DNA repair, and cell-cycle arrest under cellular stress.
- Mutations in the p53 gene are prevalent in head and neck tumors, often leading to a non-functional p53 response even in cases with wild-type p53 protein.
- Dysfunctional p53 pathways, due to mutations in interacting genes, are frequently observed in these cancers.
Purpose of the Study:
- To provide a comprehensive, up-to-date overview of the mechanisms by which p53 exerts its tumor-suppressive functions.
- To summarize current knowledge regarding the p53 family members, p63 and p73.
- To elucidate the combined role of the p53 family in influencing treatment responses.
Main Methods:
- Review of existing scientific literature on p53 function, mutations, and related pathways in cancer.
- Analysis of the roles of p53, p63, and p73 in cellular stress responses and tumor development.
- Synthesis of information regarding the therapeutic implications of targeting the p53 family.
Main Results:
- The p53 pathway is a critical determinant in preventing cancer development through various cellular mechanisms.
- Head and neck tumors frequently exhibit p53 gene mutations or functional inactivation of the p53 pathway.
- The p53 family, including p63 and p73, plays a significant role in treatment response.
Conclusions:
- The p53 family represents a key area for developing novel diagnostic, prognostic, and therapeutic strategies for head and neck cancers.
- Given the lack of other common mutations, the p53 family emerges as a primary target for future cancer research and clinical applications.
- Understanding the intricate functions of the p53 family is essential for advancing precision medicine in oncology.
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