Therapy resistance poses a significant obstacle to effective cancer treatment. Recent insights into cell plasticity as a new paradigm for understanding resistance to treatment: as cancer progresses, cancer cells experience phenotypic and molecular alterations, corporately known as cell plasticity. These alterations are caused by microenvironment factors, stochastic genetic and epigenetic changes, and/or selective pressure engendered by treatment, resulting in tumor heterogeneity and therapy resistance. Increasing evidence suggests that cancer cells display remarkable intrinsic plasticity and reversibly adapt to dynamic microenvironment conditions. Dynamic interactions between cell states and with the surrounding microenvironment form a flexible tumor ecosystem, which is able to quickly adapt to external pressure, especially treatment. Here, this review delineates the formation of cancer cell plasticity (CCP) as well as its manipulation of cancer escape from treatment. Furthermore, the intrinsic and extrinsic mechanisms driving CCP that promote the development of therapy resistance is summarized. Novel treatment strategies, e.g., inhibiting or reversing CCP is also proposed. Moreover, the review discusses the multiple lines of ongoing clinical trials globally aimed at ameliorating therapy resistance. Such advances provide directions for the development of new treatment modalities and combination therapies against CCP in the context of therapy resistance.

中文翻译：

---

治疗抵抗中的癌症可塑性：机制和新策略


治疗抵抗对有效的癌症治疗构成了重大障碍。最近对细胞可塑性的见解作为理解治疗耐药性的新范例：随着癌症的进展，癌细胞经历表型和分子改变，统称为细胞可塑性。这些改变是由微环境因素、随机遗传和表观遗传变化和/或治疗产生的选择压力引起的，导致肿瘤异质性和治疗耐药性。越来越多的证据表明，癌细胞表现出显着的内在可塑性，并可逆地适应动态微环境条件。细胞状态之间以及与周围微环境之间的动态相互作用形成了灵活的肿瘤生态系统，能够快速适应外部压力，特别是治疗。在此，这篇综述描述了癌细胞可塑性（CCP）的形成及其对癌症逃避治疗的操纵。此外，还总结了驱动 CCP 促进治疗耐药发展的内在和外在机制。还提出了新的治疗策略，例如抑制或逆转CCP。此外，该综述还讨论了全球正在进行的旨在改善治疗耐药性的多种临床试验。这些进展为在治疗耐药的情况下开发针对 CCP 的新治疗方式和联合疗法提供了方向。