p53 Modulates Radiosensitivity in Head and Neck Cancers—From Classic to Future Horizons

Abstract

p53, initially considered a tumor suppressor, has been the subject of research related to cancer treatment resistance in the last 30 years. The unfavorable response to multimodal therapy and the higher recurrence rate, despite an aggressive approach, make HNSCC a research topic of interest for improving therapeutic outcomes, even if it is only the sixth most common malignancy worldwide. New advances in molecular biology and genetics include the involvement of miRNA in the control of the p53 pathway, the understanding of mechanisms such as gain/loss of function, and the development of different methods to restore p53 function, especially for HPV-negative cases. The different ratio between mutant p53 status in the primary tumor and distant metastasis originating HNSCC may serve to select the best therapeutic target for activating an abscopal effect by radiotherapy as a “booster” of the immune system. P53 may also be a key player in choosing radiotherapy fractionation regimens. Targeting any pathway involving p53, including tumor metabolism, in particular the Warburg effect, could modulate the radiosensitivity and chemo-sensitivity of head and neck cancers.

HPV status and immunohistochemical analysis of p16, p53 and PD‑L1 expression as prognostic biomarkers in patients with squamous cell anal cancer receiving definitive radiotherapy/chemoradiotherapy

“…In the present study, p53 mutations were detected in 35.7% of the patients. Previous studies have suggested that HPV-negative tumors may be more resistant to definitive CRT due to an association between the p53 mutation and HPV-negative status (43)(44)(45)(46). Soares et al (32) detected p53 gene mutations in all HPV-negative cases and identified a significant association between poor treatment response at 6 months and the p53 mutation.…”

“…The study targeted 15 high-risk HPV types, namely HPV 16,18,31,33,35,39,45,51,52,56,58,59, 66, 67 and 68, which were grouped into HPV 16, HPV 18 and other high-risk types. In the analysis phase, patients were categorized as HPV positive or HPV negative.…”