癌症中的耐药持久细胞可塑性:更有效抗癌疗法的革命性策略。
Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies.
发表日期:2024 Aug 14
作者:
Jun He, Zejing Qiu, Jingjing Fan, Xiaohong Xie, Qinsong Sheng, Xinbing Sui
来源:
Signal Transduction and Targeted Therapy
摘要:
非遗传机制最近已成为抗癌药物耐药性的重要驱动因素。其中,耐药持久性(DTP)细胞表型吸引了越来越多的关注,并在癌症治疗耐药性中发挥着主要的非遗传作用。 DTP表型的特点是癌细胞亚群处于静止或慢细胞周期可逆状态,并对刺激呈惰性特化,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暴露,并在停药后恢复生长和增殖。 ,最终导致治疗抵抗和癌症复发。因此,尽管我们目前对这些 DTP 细胞的治疗耐药性了解仍然有限,但靶向 DTP 细胞有望为癌症患者提供新的治疗机会。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,基于不同的药物模型研究了DTP的潜在药物(包括临床前药物、老药新用途和天然产物),并探讨了DTP细胞的潜在耐药机制。讨论抗DTP治疗的必要性和可行性、相关申请形式以及推动这一新兴领域走向临床应用所需解决的未来问题。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。© 2024。作者。
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.© 2024. The Author(s).