Department of Thoracic Oncology, Sun Yat-Sen University Cancer Center, 510060 Gunagzhou, Guangdong, China.
Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 510060 Guangzhou, Guangdong, China.
Front Biosci (Landmark Ed). 2023 Sep 24;28(9):219. doi: 10.31083/j.fbl2809219.
The occurrence and development of esophageal cancer involve multiple genetic abnormalities that contribute to the malignant transformation of esophageal epithelial cells, followed by invasion and metastasis, leading to a poor outcome. Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal malignancy in East Asia, with approximately half of newly diagnosed ESCC cases occurring in China. The TP53 tumor suppressor gene mutation is one of the most common mutations in ESCC. TP53 mutations are observed even in the early phases of esophageal carcinogenesis. Normal functions of the p53 network are lost in cells of ESCC patients who harbor the mutant gene, inducing tumor development, radiation resistance, chemotherapy resistance, and immune suppression, promoting progression and metastasis, thereby resulting in an overall poor prognosis. Although clinical trials of several pharmacological compounds targeting mutational TP53 have been explored, novel approaches are still urgently required to improve the observed dismal survival. A better understanding of the role of the mutant gene in human ESCC might lead to the discovery of innovative targeted therapies to treat this malignancy.
食管癌的发生和发展涉及多个遗传异常，导致食管上皮细胞的恶性转化，随后发生侵袭和转移，导致预后不良。食管鳞状细胞癌（ESCC）是东亚食管恶性肿瘤的主要组织学亚型，约有一半新诊断的 ESCC 病例发生在中国。TP53 肿瘤抑制基因突变为 ESCC 中最常见的突变之一。即使在食管癌发生的早期阶段也可以观察到 TP53 突变。携带突变基因的 ESCC 患者的细胞中丧失了 p53 网络的正常功能，诱导肿瘤发生、辐射抵抗、化疗耐药和免疫抑制，促进进展和转移，从而导致整体预后不良。虽然已经探索了几种针对突变 TP53 的药理学化合物的临床试验，但仍迫切需要新的方法来改善观察到的不良生存。更好地了解突变基因在人类 ESCC 中的作用可能会发现治疗这种恶性肿瘤的创新靶向治疗方法。
