The emergence of drug resistance is the most substantial challenge to the effectiveness of anticancer therapies. Orthogonal approaches have revealed that a subset of cells, known as drug-tolerant ‘persister’ (DTP) cells, have a prominent role in drug resistance. Although long recognized in bacterial populations which have acquired resistance to antibiotics, the presence of DTPs in various cancer types has come to light only in the past two decades, yet several aspects of their biology remain enigmatic. Here, we delve into the biological characteristics of DTPs and explore potential strategies for tracking and targeting them. Recent findings suggest that DTPs exhibit remarkable plasticity, being capable of transitioning between different cellular states, resulting in distinct DTP phenotypes within a single tumour. However, defining the biological features of DTPs has been challenging, partly due to the complex interplay between clonal dynamics and tissue-specific factors influencing their phenotype. Moreover, the interactions between DTPs and the tumour microenvironment, including their potential to evade immune surveillance, remain to be discovered. Finally, the mechanisms underlying DTP-derived drug resistance and their correlation with clinical outcomes remain poorly understood. This Roadmap aims to provide a comprehensive overview of the field of DTPs, encompassing past achievements and current endeavours in elucidating their biology. We also discuss the prospect of future advancements in technologies in helping to unveil the features of DTPs and propose novel therapeutic strategies that could lead to their eradication.

耐药性的出现是对抗癌治疗有效性的最大挑战。正交方法表明，一个细胞亚群，称为耐药“持久性”（DTP） 细胞，在耐药性中起着重要作用。尽管在获得抗生素耐药性的细菌种群中早已得到认可，但 DTP 在各种癌症类型中的存在直到最近二十年才被发现，但其生物学的几个方面仍然是个谜。在这里，我们深入研究了 DTP 的生物学特性，并探索了追踪和靶向它们的潜在策略。最近的研究结果表明，DTP 表现出显着的可塑性，能够在不同的细胞状态之间转换，从而在单个肿瘤内产生不同的 DTP 表型。然而，定义 DTP 的生物学特征一直具有挑战性，部分原因是克隆动力学和影响其表型的组织特异性因素之间存在复杂的相互作用。此外，DTP 与肿瘤微环境之间的相互作用，包括它们逃避免疫监视的潜力，仍有待发现。最后，DTP 衍生的耐药机制及其与临床结果的相关性仍然知之甚少。本路线图旨在提供 DTP 领域的全面概述，包括过去的成就和当前在阐明其生物学方面的努力。我们还讨论了技术未来进步的前景，以帮助揭示 DTP 的特征，并提出可能导致其根除的新型治疗策略。