Translational Bioinformatics, Center for Informatics, Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Duarte, CA 91010, USA.
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010, USA.
Trends Cancer. 2021 Apr;7(4):323-334. doi: 10.1016/j.trecan.2021.01.009. Epub 2021 Feb 20.
Drug resistance is a major impediment in cancer. Although it is generally thought that acquired drug resistance is due to genetic mutations, emerging evidence indicates that nongenetic mechanisms also play an important role. Resistance emerges through a complex interplay of clonal groups within a heterogeneous tumor and the surrounding microenvironment. Traits such as phenotypic plasticity, intercellular communication, and adaptive stress response, act in concert to ensure survival of intermediate reversible phenotypes, until permanent, resistant clones can emerge. Understanding the role of group behavior, and the underlying nongenetic mechanisms, can lead to more efficacious treatment designs and minimize or delay emergence of resistance.
耐药性是癌症的主要障碍。虽然人们普遍认为获得性耐药性是由于基因突变引起的，但新出现的证据表明，非遗传机制也起着重要作用。耐药性通过异质性肿瘤内的克隆群体与周围微环境之间的复杂相互作用而出现。表型可塑性、细胞间通讯和适应性应激反应等特性协同作用，以确保中间可逆表型的存活，直到永久性耐药克隆能够出现。了解群体行为的作用和潜在的非遗传机制，可以导致更有效的治疗设计，并最小化或延迟耐药性的出现。
