Emran Talha Bin, Shahriar Asif, Mahmud Aar Rafi, Rahman Tanjilur, Abir Mehedy Hasan, Siddiquee Mohd Faijanur-Rob, Ahmed Hossain, Rahman Nova, Nainu Firzan, Wahyudin Elly, Mitra Saikat, Dhama Kuldeep, Habiballah Mahmoud M, Haque Shafiul, Islam Ariful, Hassan Mohammad Mahmudul
Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, Bangladesh.
Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh.
Front Oncol. 2022 Jun 23;12:891652. doi: 10.3389/fonc.2022.891652. eCollection 2022.
Cancer is one of the leading causes of death worldwide. Several treatments are available for cancer treatment, but many treatment methods are ineffective against multidrug-resistant cancer. Multidrug resistance (MDR) represents a major obstacle to effective therapeutic interventions against cancer. This review describes the known MDR mechanisms in cancer cells and discusses ongoing laboratory approaches and novel therapeutic strategies that aim to inhibit, circumvent, or reverse MDR development in various cancer types. In this review, we discuss both intrinsic and acquired drug resistance, in addition to highlighting hypoxia- and autophagy-mediated drug resistance mechanisms. Several factors, including individual genetic differences, such as mutations, altered epigenetics, enhanced drug efflux, cell death inhibition, and various other molecular and cellular mechanisms, are responsible for the development of resistance against anticancer agents. Drug resistance can also depend on cellular autophagic and hypoxic status. The expression of drug-resistant genes and the regulatory mechanisms that determine drug resistance are also discussed. Methods to circumvent MDR, including immunoprevention, the use of microparticles and nanomedicine might result in better strategies for fighting cancer.
癌症是全球主要死因之一。有多种治疗方法可用于癌症治疗,但许多治疗方法对多药耐药性癌症无效。多药耐药性(MDR)是有效治疗癌症的主要障碍。本综述描述了癌细胞中已知的多药耐药机制,并讨论了旨在抑制、规避或逆转各种癌症类型中多药耐药性发展的现有实验室方法和新型治疗策略。在本综述中,我们除了强调缺氧和自噬介导的耐药机制外,还讨论了内在和获得性耐药性。包括个体遗传差异(如突变、表观遗传学改变、药物外排增强、细胞死亡抑制)以及各种其他分子和细胞机制在内的几个因素是导致对抗癌药物产生耐药性的原因。耐药性还可能取决于细胞自噬和缺氧状态。文中还讨论了耐药基因的表达以及决定耐药性的调控机制。规避多药耐药性的方法,包括免疫预防、使用微粒和纳米药物,可能会产生更好的抗癌策略。