Department of Dermatology, University of Colorado School of Medicine, Aurora, CO, USA.
The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, OLD, Australia.
Theranostics. 2020 May 15;10(14):6261-6277. doi: 10.7150/thno.42523. eCollection 2020.
Despite the recent advances in the treatment of cancers, acquired drug resistance remains a major challenge in cancer management. While earlier studies suggest Darwinian factors driving acquired drug resistance, recent studies point to a more dynamic process involving phenotypic plasticity and tumor heterogeneity in the evolution of acquired drug resistance. Chronic stress after drug treatment induces intrinsic cellular reprogramming and cancer stemness through a slow-cycling persister state, which subsequently drives cancer progression. Both epigenetic and metabolic mechanisms play an important role in this dynamic process. In this review, we discuss how epigenetic and metabolic reprogramming leads to stress-induced phenotypic plasticity and acquired drug resistance, and how the two reprogramming mechanisms crosstalk with each other.
尽管癌症治疗在最近取得了进展，但获得性药物耐药性仍然是癌症管理中的一个主要挑战。虽然早期的研究表明达尔文因素驱动了获得性药物耐药性，但最近的研究表明，在获得性药物耐药性的演变过程中，涉及表型可塑性和肿瘤异质性的更动态的过程。药物治疗后慢性应激通过慢循环持久状态诱导内在细胞重编程和癌症干性，随后推动癌症进展。表观遗传和代谢机制在这个动态过程中都起着重要作用。在这篇综述中，我们讨论了表观遗传和代谢重编程如何导致应激诱导的表型可塑性和获得性药物耐药性，以及这两种重编程机制如何相互作用。
