Kachalaki Saeed, Ebrahimi Mina, Mohamed Khosroshahi Leila, Mohammadinejad Sina, Baradaran Behzad
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Eur J Pharm Sci. 2016 Jun 30;89:20-30. doi: 10.1016/j.ejps.2016.03.025. Epub 2016 Apr 16.
The effectiveness of chemotherapy is one of the main challenges in cancer treatment and resistance to classic drugs and traditional treatment processes is an obstacle to this goal. Drug resistance that may be inherent or adventitious can cause poor treatment outcome and tumor relapse. In most cases, resistance to a drug can lead to resistance to many other drugs structure and function of which is not necessarily similar to the first drug. This phenomenon is the main mechanism behind failure of many of metastatic cancers. There are various molecular mechanisms involved in multidrug resistance, including change in the activity of membrane transporters (such as ABC transporters), increase of drug metabolism, change of the target enzyme (such as mutations that change thymidylate synthase and topoisomerases), promotion of DNA damage repair, and escape from drug induced apoptosis. Clinical and laboratory investigations on biomarkers involved in the response to chemotherapy have characterized the key factors behind the failure of treatments. Knowing the molecular factors involved in drug resistance may help us to develop new strategies for more promising chemotherapy and reduce the rate of relapse. In this brief review, molecular mechanisms and tumor microenvironment leading to decreased drug sensitivity, and strategies of reversing drug resistance are described.
化疗的有效性是癌症治疗中的主要挑战之一，对经典药物和传统治疗方法产生耐药性是实现这一目标的障碍。可能是内在的或偶然产生的耐药性会导致治疗效果不佳和肿瘤复发。在大多数情况下，对一种药物的耐药性会导致对许多其他药物产生耐药性，而这些药物的结构和功能不一定与第一种药物相似。这种现象是许多转移性癌症治疗失败的主要机制。多药耐药涉及多种分子机制，包括膜转运蛋白（如ABC转运蛋白）活性的改变、药物代谢增加、靶酶的变化（如改变胸苷酸合成酶和拓扑异构酶的突变）、DNA损伤修复的促进以及逃避药物诱导的细胞凋亡。对化疗反应中涉及的生物标志物的临床和实验室研究已经明确了治疗失败背后的关键因素。了解与耐药性相关的分子因素可能有助于我们制定更有前景的化疗新策略，并降低复发率。在这篇简要综述中，描述了导致药物敏感性降低的分子机制和肿瘤微环境，以及逆转耐药性的策略。
