The role of TP53 mutations in oral cancer: molecular mechanisms and prognostic implications

A comprehensive review highlights how TP53 mutations contribute to oral cancer development, treatment resistance, and poor patient outcomes. The study summarizes emerging therapeutic approaches, including mutant p53 reactivation, synthetic lethality, and immunotherapy-based strategies, providing new perspectives for precision medicine in oral cancer.

Oral squamous cell carcinoma (OSCC) is among the most common malignancies of the head and neck region and remains associated with significant morbidity and mortality worldwide. Despite advances in surgery, radiotherapy, and chemotherapy, long-term survival rates remain unsatisfactory, largely due to tumor recurrence, metastasis, and therapeutic resistance.

In a recent review published in Advanced Cancer Research, researchers systematically summarized current knowledge regarding TP53 mutations in oral cancer and their implications for prognosis and targeted therapy.

TP53 encodes the tumor suppressor protein p53, often referred to as the “guardian of the genome.” Under physiological conditions, p53 protects cells by regulating cell-cycle arrest, DNA repair, apoptosis, and genomic stability. However, TP53 mutations are detected in approximately 40–80% of oral squamous cell carcinomas and represent one of the most frequent genetic alterations in this disease.

The review demonstrates that TP53 mutations promote oral cancer progression through both loss-of-function and gain-of-function mechanisms. Mutant p53 proteins not only lose their tumor-suppressive activities but may also acquire oncogenic properties that stimulate tumor growth, invasion, metastasis, and resistance to chemotherapy and radiotherapy.

Key findings include:

• TP53 mutations are strongly associated with advanced tumor stage, lymph node metastasis, therapy resistance, and poor prognosis.

• Mutant p53 drives multiple oncogenic pathways, including epithelial-mesenchymal transition (EMT) and PI3K/AKT/mTOR signaling.

• TP53 mutation status may serve as an important biomarker for risk stratification and personalized treatment planning.

• Novel therapeutic strategies are emerging, including mutant p53 reactivation, synthetic lethality-based treatments, and immune-targeted combination therapies.

The authors further emphasize that integrating genomic profiling, single-cell technologies, and artificial intelligence-driven analyses may improve the understanding of TP53 mutation heterogeneity and accelerate the development of precision medicine approaches for oral cancer.

This review provides a comprehensive framework linking TP53 biology to clinical outcomes and therapeutic opportunities, highlighting mutant p53 as both a prognostic biomarker and a promising therapeutic target in oral cancer.

Citation: Ma L, Liu Z, Huang K, Xiao J, Zhao S, et al. The role of TP53 mutations in oral cancer: molecular mechanisms and prognostic implications. Adv. Cancer Res. 2026(2):0008, https://doi.org/10.55092/acr20260008.