Passaro Eugenia, Papulino Chiara, Chianese Ugo, Toraldo Antonella, Congi Raffaella, Del Gaudio Nunzio, Nicoletti Maria Maddalena, Benedetti Rosaria, Altucci Lucia
Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Biogem Institute of Molecular and Genetic Biology, 83031 Ariano Irpino, Italy.
Cancers (Basel). 2021 Dec 14;13(24):6280. doi: 10.3390/cancers13246280.
Autophagy is an essential intracellular catabolic mechanism involved in the degradation and recycling of damaged organelles regulating cellular homeostasis and energy metabolism. Its activation enhances cellular tolerance to various stresses and is known to be involved in drug resistance. In cancer, autophagy has a dual role in either promoting or blocking tumorigenesis, and recent studies indicate that epigenetic regulation is involved in its mechanism of action in this context. Specifically, the ubiquitin-binding histone deacetylase (HDAC) enzyme HDAC6 is known to be an important player in modulating autophagy. Epigenetic modulators, such as HDAC inhibitors, mediate this process in different ways and are already undergoing clinical trials. In this review, we describe current knowledge on the role of epigenetic modifications, particularly HDAC-mediated modifications, in controlling autophagy in cancer. We focus on the controversy surrounding their ability to promote or block tumor progression and explore the impact of HDAC6 inhibitors on autophagy modulation in cancer. In light of the fact that targeted drug therapy for cancer patients is attracting ever increasing interest within the research community and in society at large, we discuss the possibility of using HDAC6 inhibitors as adjuvants and/or in combination with conventional treatments to overcome autophagy-related mechanisms of resistance.
自噬是一种重要的细胞内分解代谢机制，参与受损细胞器的降解和再循环，调节细胞内稳态和能量代谢。其激活增强细胞对各种应激的耐受性，并且已知与耐药性有关。在癌症中，自噬在促进或阻断肿瘤发生方面具有双重作用，最近的研究表明，表观遗传调控参与了其在这种情况下的作用机制。具体而言，已知泛素结合组蛋白去乙酰化酶（HDAC）HDAC6是调节自噬的重要参与者。表观遗传调节剂，如HDAC抑制剂，以不同方式介导这一过程，并且已经在进行临床试验。在这篇综述中，我们描述了关于表观遗传修饰，特别是HDAC介导的修饰，在控制癌症自噬中的作用的当前知识。我们关注围绕它们促进或阻断肿瘤进展能力的争议，并探讨HDAC6抑制剂对癌症自噬调节的影响。鉴于针对癌症患者的靶向药物治疗在研究界和整个社会中引起了越来越多的关注，我们讨论了使用HDAC6抑制剂作为佐剂和/或与传统治疗联合使用以克服自噬相关耐药机制的可能性。
