Department of Pathology, The First Affiliated Hospital of Soochow University, Soochow University, 215006 Suzhou, Jiangsu, China.
Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, 215006 Suzhou, Jiangsu, China.
Front Biosci (Landmark Ed). 2024 Jul 25;29(7):272. doi: 10.31083/j.fbl2907272.
The p53, a pivotal tumor suppressor, regulates various cellular responses, including DNA repair and apoptosis. Normally, p53 levels are low due to murine double minute clone 2 (MDM2) mediated polyubiquitination. However, stress signals disrupt p53-MDM2 interaction, stabilizing p53 and activating target genes. Dysfunctional p53 is common in cancers, especially colorectal cancer (CRC), with mutations in 43% of tumors. These mutations impair wild-type p53 function or confer novel activities, promoting cancer progression. Despite drugs targeting p53 entering trials, understanding wild-type and mutant p53 functions is crucial for novel CRC therapies. P53 mutations not only impact DNA repair and apoptosis but also play a crucial role in tumor immunotherapy. While rendering tumors resistant to chemotherapy, p53 mutations provide opportunities for immunotherapy due to neoantigen-rich tumors. Additionally, p53 mutations influence tumor microenvironment cells, such as fibroblasts and immunosuppressive cells, through p53-mediated signaling pathways. Investigating p53 mutations in tumor therapy is vital for personalized medicine and immunotherapy. In cancer treatment research, scientists explore drugs and strategies to restore or enhance p53 function. Targeting wild-type p53 aims to restore DNA repair and cell cycle control, while targeting mutant p53 seeks new drugs to inhibit its detrimental effects, advancing tumor treatment. Understanding p53 drugs and strategies is crucial for cancer therapy progress.
p53 是一种重要的肿瘤抑制因子，调节多种细胞反应，包括 DNA 修复和细胞凋亡。正常情况下，由于鼠双微体 2（MDM2）介导的多泛素化，p53 水平较低。然而，应激信号会破坏 p53-MDM2 相互作用，稳定 p53 并激活靶基因。p53 功能失调在癌症中很常见，尤其是结直肠癌（CRC），其中 43%的肿瘤存在 突变。这些突变会损害野生型 p53 的功能或赋予其新的活性，从而促进癌症的进展。尽管针对 p53 的药物已进入临床试验，但了解野生型和突变型 p53 的功能对于新型 CRC 治疗至关重要。p53 突变不仅影响 DNA 修复和细胞凋亡，而且在肿瘤免疫治疗中也起着至关重要的作用。虽然 p53 突变使肿瘤对化疗产生耐药性，但由于富含新抗原的肿瘤，p53 突变为免疫治疗提供了机会。此外，p53 突变通过 p53 介导的信号通路影响肿瘤微环境细胞，如成纤维细胞和免疫抑制细胞。研究肿瘤治疗中的 p53 突变对于个性化医学和免疫治疗至关重要。在癌症治疗研究中，科学家探索恢复或增强 p53 功能的药物和策略。靶向野生型 p53 旨在恢复 DNA 修复和细胞周期控制，而靶向突变型 p53 则寻求新的药物来抑制其有害影响，从而推进肿瘤治疗。了解 p53 药物和策略对于癌症治疗进展至关重要。
