Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Front Biosci (Landmark Ed). 2024 Jul 2;29(7):242. doi: 10.31083/j.fbl2907242.
Autophagy is an evolutionarily conserved process in which intracellular macromolecules are degraded in a lysosomal-dependent manner. It is central to cellular energy homeostasis and to quality control of intracellular components. A decline in autophagic activity is associated with aging, and contributes to the development of various age-associated pathologies, including cancer. There is an ongoing need to develop chemotherapeutic agents to improve morbidity and mortality for those diagnosed with cancer, as well as to decrease the cost of cancer care. Autophagic programs are altered in cancer cells to support survival in genetically and metabolically unstable environments, making autophagy an attractive target for new chemotherapy. Antiretroviral drugs, which have dramatically increased the life- and health spans of people with human immunodeficiency virus (HIV) (PWH), have offered promise in the treatment of cancer. One mechanism underlying the antineoplastic effects of antiretroviral drugs is the alteration of cancer cell autophagy that can potentiate cell death. Antiretroviral drugs could be repurposed into the cancer chemotherapy arsenal. A more complete understanding of the impact of antiretroviral drugs on autophagy is essential for effective repurposing. This review summarizes our knowledge of the effects of antiretroviral drugs on autophagy as potential adjunctive chemotherapeutic agents, and highlights gaps to be addressed to reposition antiretroviral drugs into the antineoplastic arsenal successfully.
自噬是一种进化上保守的过程，其中细胞内大分子通过溶酶体依赖性方式降解。它是细胞能量稳态和细胞内成分质量控制的核心。自噬活性的下降与衰老有关，并导致各种与年龄相关的病理学的发展，包括癌症。为了改善诊断为癌症的患者的发病率和死亡率，并降低癌症治疗的成本，人们一直在需要开发化疗药物。自噬程序在癌细胞中发生改变，以支持在遗传和代谢不稳定的环境中存活，从而使自噬成为新化疗的有吸引力的靶标。抗逆转录病毒药物（antiretroviral drugs）极大地提高了患有人类免疫缺陷病毒（HIV）的人的寿命和健康寿命（PWH），在癌症治疗中也显示出了希望。抗逆转录病毒药物抗肿瘤作用的一种机制是改变癌细胞自噬，从而增强细胞死亡。抗逆转录病毒药物可以重新用于癌症化疗武器库。更全面地了解抗逆转录病毒药物对自噬的影响对于有效重新定位至关重要。这篇综述总结了我们对抗逆转录病毒药物对自噬作为潜在辅助化疗药物的影响的认识，并强调了为成功将抗逆转录病毒药物重新定位到抗肿瘤武器库中而需要解决的差距。
