Rueff José, Rodrigues António Sebastião
Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Rua Câmara Pestana 6, 1150-008, Lisbon, Portugal.
Methods Mol Biol. 2016;1395:1-18. doi: 10.1007/978-1-4939-3347-1_1.
Cancer drug resistance leading to therapeutic failure in the treatment of many cancers encompasses various mechanisms and may be intrinsic relying on the patient's genetic makeup or be acquired by tumors that are initially sensitive to cancer drugs. All in all, it may be responsible for treatment failure in over 90 % of patients with metastatic cancer. Cancer drug resistance, in particular acquired resistance, may stem from the micro-clonality/micro-genetic heterogeneity of the tumors whereby, among others, the following mechanisms may entail resistance: altered expression of drug influx/efflux transporters in the tumor cells mediating lower drug uptake and/or greater efflux of the drug; altered role of DNA repair and impairment of apoptosis; role of epigenomics/epistasis by methylation, acetylation, and altered levels of microRNAs leading to alterations in upstream or downstream effectors; mutation of drug targets in targeted therapy and alterations in the cell cycle and checkpoints; and tumor microenvironment that are briefly reviewed.
癌症耐药性导致许多癌症治疗失败，其涉及多种机制，可能是依赖患者基因构成的内在耐药性，也可能是最初对癌症药物敏感的肿瘤获得性耐药。总之，它可能导致超过90%的转移性癌症患者治疗失败。癌症耐药性，尤其是获得性耐药，可能源于肿瘤的微克隆性/微基因异质性，其中以下机制可能导致耐药：肿瘤细胞中药物流入/流出转运蛋白的表达改变，介导较低的药物摄取和/或更多的药物流出；DNA修复作用改变和细胞凋亡受损；通过甲基化、乙酰化以及微小RNA水平改变导致上游或下游效应器改变的表观基因组学/上位性作用；靶向治疗中药物靶点的突变以及细胞周期和检查点的改变；以及肿瘤微环境，本文将对其进行简要综述。
