Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China.
Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China.
Signal Transduct Target Ther. 2024 Aug 14;9(1):209. doi: 10.1038/s41392-024-01891-4.
Non-genetic mechanisms have recently emerged as important drivers of anticancer drug resistance. Among these, the drug tolerant persister (DTP) cell phenotype is attracting more and more attention and giving a predominant non-genetic role in cancer therapy resistance. The DTP phenotype is characterized by a quiescent or slow-cell-cycle reversible state of the cancer cell subpopulation and inert specialization to stimuli, which tolerates anticancer drug exposure to some extent through the interaction of multiple underlying mechanisms and recovering growth and proliferation after drug withdrawal, ultimately leading to treatment resistance and cancer recurrence. Therefore, targeting DTP cells is anticipated to provide new treatment opportunities for cancer patients, although our current knowledge of these DTP cells in treatment resistance remains limited. In this review, we provide a comprehensive overview of the formation characteristics and underlying drug tolerant mechanisms of DTP cells, investigate the potential drugs for DTP (including preclinical drugs, novel use for old drugs, and natural products) based on different medicine models, and discuss the necessity and feasibility of anti-DTP therapy, related application forms, and future issues that will need to be addressed to advance this emerging field towards clinical applications. Nonetheless, understanding the novel functions of DTP cells may enable us to develop new more effective anticancer therapy and improve clinical outcomes for cancer patients.
非遗传机制最近已成为抗癌药物耐药性的重要驱动因素。在这些机制中，耐药持续细胞（DTP）表型越来越受到关注，并在癌症治疗耐药性中赋予了主要的非遗传作用。DTP 表型的特征是癌细胞亚群处于静止或慢细胞周期可逆状态，对刺激具有惰性专业化，通过多种潜在机制的相互作用，在一定程度上耐受抗癌药物的暴露，并在停药后恢复生长和增殖，最终导致治疗耐药和癌症复发。因此，靶向 DTP 细胞有望为癌症患者提供新的治疗机会，尽管我们对这些治疗耐药性中的 DTP 细胞的了解仍然有限。在这篇综述中，我们全面概述了 DTP 细胞的形成特征和潜在的耐药机制，根据不同的药物模型，研究了针对 DTP 的潜在药物（包括临床前药物、旧药的新用途和天然产物），并讨论了抗-DTP 治疗的必要性和可行性、相关的应用形式以及未来需要解决的问题，以推动这一新兴领域走向临床应用。尽管如此，了解 DTP 细胞的新功能可能使我们能够开发新的更有效的抗癌疗法，并改善癌症患者的临床结果。
