头颈部鳞状细胞癌(HNSCC)是世界上最广泛的恶性肿瘤之一。p53作为转录因子,可以通过激活许多靶基因的表达来发挥其在肿瘤抑制中的作用。然而,p53是最常见的突变基因之一,经常有错义突变。这些错义突变是导致DNA结合结构域中的氨基酸取代的核苷酸取代。HNSCC中的大多数p53突变是错义突变,p53的突变率达到65-85%。p53突变不仅抑制了p53的肿瘤抑制功能,还提供了促进肿瘤复发的新功能。称为函数增益(GOF)。本研究集中在HNSCC中p53突变的患病率和临床相关性。并进一步描述了突变型p53是如何积累的。此外,HNSCC中的突变型p53可以与蛋白质相互作用,RNA,和外泌体对增殖产生影响,迁移,入侵,免疫抑制,和新陈代谢。最后,已经提出了几种治疗策略来消除突变型p53的肿瘤促进功能;这些策略包括将突变型p53重新激活为野生型p53,诱导突变型p53降解,突变型p53的合成致死率的增强,以及免疫疗法的治疗。由于HNSCC中p53突变的频率很高,进一步了解突变型p53的机制可能为HNSCC患者的靶向治疗提供潜在应用。
Head and neck squamous cell carcinoma (HNSCC) is one of the most widespread malignancies worldwide. p53, as a transcription factor, can play its role in tumor suppression by activating the expression of numerous target genes. However, p53 is one of the most commonly mutated genes, which frequently harbors missense mutations. These missense mutations are nucleotide substitutions that result in the substitution of an amino acid in the DNA binding domain. Most p53 mutations in HNSCC are missense mutations and the mutation rate of p53 reaches 65‑85%. p53 mutation not only inhibits the tumor suppressive function of p53 but also provides novel functions to facilitate tumor recurrence, called gain‑of‑function (GOF). The present study focused on the prevalence and clinical relevance of p53 mutations in HNSCC, and further described how mutant p53 accumulates. Moreover, mutant p53 in HNSCC can interact with proteins, RNA, and exosomes to exert effects on proliferation, migration, invasion, immunosuppression, and metabolism. Finally, several treatment strategies have been proposed to abolish the tumor‑promoting function of mutant p53; these strategies include reactivation of mutant p53 into wild‑type p53, induction of mutant p53 degradation, enhancement of the synthetic lethality of mutant p53, and treatment with immunotherapy. Due to the high frequency of p53 mutations in HNSCC, a further understanding of the mechanism of mutant p53 may provide potential applications for targeted therapy in patients with HNSCC.