Sblano Sabina, Boccarelli Angelina, Deruvo Caterina, La Spada Gabriella, de Candia Modesto, Purgatorio Rosa, Altomare Cosimo Damiano, Catto Marco
Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125, Bari, Italy.
Department of Precision and Regenerative Medicine and Ionian Area, School of Medicine, University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124, Bari, Italy.
Eur J Med Chem. 2025 Feb 5;283:117159. doi: 10.1016/j.ejmech.2024.117159. Epub 2024 Dec 15.
Drug resistance in cancer is determined by genetic mutations and adaptations of tumor cells to drug treatments, raising a challenge in the treatment of cancer. Factors such as prolonged drug exposure, genetic variability among patients, and tumor heterogeneity have been established as contributors to rising incidence of drug resistance, prompting ongoing research into alternative therapies and combination treatments to overcome this challenge. Monoamine oxidases (MAOs), including both isoforms MAO-A and MAO-B, are mitochondrial enzymes responsible for the catabolism of monoamine neurotransmitters such as dopamine, norepinephrine, and serotonin. While these enzymes play a pivotal role in the nervous system, their role in tumorigenesis has garnered increasing attention in the last years. Recent studies, in fact, have highlighted the potential of MAO inhibitors (MAOIs) as antitumor agents, emphasizing their use as standalone treatments or in synergy with traditional anticancer therapies, focusing on pathways involved in tumorigenesis. This review aims to provide a comprehensive overview of MAOIs currently under study for their potential antitumor activity, focusing on their structural characteristics, mechanisms of action, and efficacy in preclinical and clinical settings, referencing key articles in the field.
癌症中的耐药性由肿瘤细胞的基因突变和对药物治疗的适应性决定,这给癌症治疗带来了挑战。长期药物暴露、患者间的基因变异性以及肿瘤异质性等因素已被确认为导致耐药性发生率上升的因素,促使人们持续研究替代疗法和联合治疗以应对这一挑战。单胺氧化酶(MAO),包括MAO - A和MAO - B两种亚型,是负责多巴胺、去甲肾上腺素和血清素等单胺神经递质分解代谢的线粒体酶。虽然这些酶在神经系统中起关键作用,但它们在肿瘤发生中的作用在过去几年中受到了越来越多的关注。事实上,最近的研究强调了MAO抑制剂(MAOI)作为抗肿瘤药物的潜力,强调其作为单一疗法或与传统抗癌疗法协同使用,重点关注参与肿瘤发生的途径。本综述旨在全面概述目前正在研究其潜在抗肿瘤活性的MAOI,重点关注其结构特征、作用机制以及在临床前和临床环境中的疗效,并引用该领域的关键文章。