Strategies for Anticancer Treatment in p53-Mutated Head and Neck Squamous Cell Carcinoma

Abstract

This Opinion summarizes the strategies for anticancer treatment in p53-mutated head and neck squamous cell carcinoma (HNSCC). It examines six strategies for anticancer treatment in p53-mutated HNSCC: 1. direct reactivation of mutated p53; 2. activation of p63; 3. activation of p73; 4. degradation of mutated p53; 5. blocking the p53-regulated oncogenic microRNA; and 6. blocking the p53-regulated oncogenic long non-coding RNA. Since HNSCC has a high p53 mutation rate compared to other types of cancers, these strategies for combating p53-mutated HNSCC may prove useful for generating new ideas or methods for developing treatments for other cancers with p53 mutations. This article also explores other factors that may impact the effectiveness of anticancer therapies in p53-mutated HNSCC.

Keywords: HNSCC; head and neck cancer; mutation; p53.

Figure 1

p53 mutation rates in different cancers. According to the cBioPortal database (cbioportal.org, accessed on 1 February 2025) [1], head and neck squamous cell carcinoma (HNSCC) has a p53 mutation rate of 68.26%, ranking fourth among all cancer types.

Figure 2

Strategies for targeting p53-mutated HNSCC. Six key strategies have been explored to target p53-mutated HNSCC. (1) Direct reactivation of mutant p53: APR-246 binds to and reactivates mutant p53, restoring its tumor-suppressor function. (2) Activation of p63: lovastatin and doxorubicin can activate p63 in p53-mutated HNSCC cells, leading to cancer cell death. (3) Activation of p73: chlorophyllides, RETRA, NSC59984, and the miRNA-193a-5p inhibitor activate p73 in p53-mutated HNSCC cells, inducing apoptosis. (4) Degradation of mutant p53: AUY922 and shRNA targeting DNAJA1 (shDNAJA1) promote the degradation of mutant p53, reducing oncogenic properties such as cell migration and colony formation in HNSCC cells. (5) Blocking mutant p53-regulated oncogenic microRNA: mutant p53 upregulates oncogenic miR-182-5p, inhibiting miR-182-5p reduces oncogenic properties, including cell proliferation and migration, in p53-mutated HNSCC cells. (6) Blocking mutant p53-regulated oncogenic long non-coding RNA: downregulation of the long non-coding RNA lncMIR205HG impairs multiple oncogenic properties, including cell proliferation, migration, and colony formation, in p53-mutated HNSCC cells.