Cancer continues to be a leading threat to human health and life. Resistance to anti-cancer drugs is a major impediment towards efficacious cancer treatment. p53 mutations play an important role in cancer cell resistance to chemotherapeutic drugs. The frequency of p53-based chemoresistance is highly associated with the chemical properties of the anticancer drug, the cellular drug target, the biological function being blocked by the chemotherapeutic agent, the genomic instability and alterations of the tumor, as well as its differentiation state. The p53-based molecular mechanisms of anticancer drug resistance are insufficiently understood. With a clear focus on the role of p53 mutations in anticancer drug resistance, the present article reviews the biological structure and function of p53, its regulatory mechanisms, as well as the molecular mechanisms underlying p53 mutation-dependent chemoresistance and possible modalities to surmount this drug resistance. We specifically discuss the roles of p53 in the development of chemoresistance to classical cytotoxic agents including for example cisplatin, doxorubicin, 5-fluorouracil, temozolomide, and paclitaxel. It is expected that the clinical manifestation of drug resistance can be integrated with data obtained from molecular multi-omics analyses addressing the alterations provoked by p53-driven resistance to discover the altered networks in these drug resistant tumors. Thus, novel drugs targeting mutant p53 or mutant p53-based dysregulated pathways, could be developed that may overcome well-defined mutant p53-mediated chemoresistance. Thus, an in-depth understanding of the p53-driven resistance modalities could facilitate the development of novel targeted antitumor drugs and strategies aimed at enhancing the efficacy of current cancer therapeutics.

癌症仍然是对人类健康和生命的主要威胁。对抗癌药的耐药性是有效治疗癌症的主要障碍。p53突变在癌细胞对化学治疗药物的耐药性中起重要作用。基于p53的化学抗药性的频率与抗癌药的化学性质，细胞药物靶标，生物功能被化疗药物所阻断，肿瘤的基因组不稳定性和改变及其分化状态高度相关。基于p53的抗癌药物耐药性分子机制尚不充分了解。明确关注p53突变在抗癌药耐药性中的作用，本文综述了p53的生物学结构和功能，其调节机制，以及p53突变依赖性化学抗性的分子机制以及克服这种耐药性的可能方式。我们具体讨论了p53在对经典细胞毒性药物（包括顺铂，阿霉素，5-氟尿嘧啶，替莫唑胺和紫杉醇）的化学耐药性发展中的作用。预期可以将耐药性的临床表现与分子多组学分析获得的数据相结合，以解决由p53驱动的耐药性引起的变化，从而发现这些耐药性肿瘤中发生变化的网络。因此，可以开发靶向突变体p53或基于突变体p53的失调途径的新药，这些药物可以克服明确定义的突变体p53介导的化学耐药性。因此，