在肿瘤生物学中，肿瘤内异质性可谓是目前最研究的话题之一，因为它是有效癌症治疗的重要障碍之一。由于肿瘤细胞在遗传、表观遗传和表型水平上高度多样化，因此肿瘤内异质性可以被认为是化疗效果无效和肿瘤复发的重要贡献因素之一。基于癌细胞群体中具有不同细胞周期动力学和行为的异质亚群在癌症进展和治疗过程中的作用，我们在此旨在建立对肿瘤细胞适应治疗的全面定义。我们讨论了两个并行但又不同的肿瘤细胞亚群，它们在减轻化疗效果方面起着关键作用：“耐药”亚群和“耐受”亚群。此外，本综述还强调了细胞周期静止期作为癌细胞的一种生存机制的影响。了解细胞进入静止期的机制不仅提供了对癌干细胞（CSCs）和其在治疗中根据细胞周期状态的双重和相互作用功能的深入洞察，还证明处于细胞周期静止期的CSCs、上皮间质转化细胞、循环肿瘤细胞（CTCs）和播散肿瘤细胞（DTCs）在肿瘤细胞周期异质性观点中具有多重生物学联系。总体而言，增加对细胞周期异质性知识的了解是识别新的治疗解决方案的关键，这一新兴理念可能为我们提供预防可怕的癌症复发的新机会。© 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology, as it represents a major obstacle to effective cancer treatment. Since tumor cells are highly diverse at genetic, epigenetic, and phenotypic levels, intra-tumor heterogeneity can be assumed as an important contributing factor to the nullification of chemotherapeutic effects, and recurrence of the tumor. Based on the role of heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics and behavior during cancer progression and treatment; herein, we aim to establish a comprehensive definition for adaptation of neoplastic cells against therapy. We discuss two parallel and yet distinct subpopulations of tumor cells that play pivotal roles in reducing the effects of chemotherapy: "resistant" and "tolerant" populations. Furthermore, this review also highlights the impact of the quiescent phase of the cell cycle as a survival mechanism for cancer cells. Beyond understanding the mechanisms underlying the quiescence, it provides an insightful perspective on cancer stem cells (CSCs) and their dual and intertwined functions based on their cell cycle state in response to treatment. Moreover, CSCs, epithelial-mesenchymal transformed cells, circulating tumor cells (CTCs), and disseminated tumor cells (DTCs), which are mostly in a quiescent state of the cell cycle are proved to have multiple biological links and can be implicated in our viewpoint of cell cycle heterogeneity in tumors. Overall, increasing our knowledge of cell cycle heterogeneity is a key to identifying new therapeutic solutions, and this emerging concept may provide us with new opportunities to prevent the dreadful cancer recurrence.© 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.