Bioinformatics and Functional Genomics Group, Cancer Research Center (CiC-IBMCC, CSIC/USAL/IBSAL), Consejo Superior de Investigaciones Científicas (CSIC), University of Salamanca (USAL), Salamanca, Spain.
Division of Molecular Biology, Ruđer Bošković Institute, Bijenička 54, 10000, Zagreb, Croatia.
Arch Toxicol. 2021 Jul;95(7):2279-2297. doi: 10.1007/s00204-021-03063-7. Epub 2021 May 18.
Over the last decade, important clinical benefits have been achieved in cancer patients by using drug-targeting strategies. Nevertheless, drug resistance is still a major problem in most cancer therapies. Epithelial-mesenchymal plasticity (EMP) and tumour microenvironment have been described as limiting factors for effective treatment in many cancer types. Moreover, epithelial-to-mesenchymal transition (EMT) has also been associated with therapy resistance in many different preclinical models, although limited evidence has been obtained from clinical studies and clinical samples. In this review, we particularly deepen into the mechanisms of which intermediate epithelial/mesenchymal (E/M) states and its interconnection to microenvironment influence therapy resistance. We also describe how the use of bioinformatics and pharmacogenomics will help to figure out the biological impact of the EMT on drug resistance and to develop novel pharmacological approaches in the future.
在过去的十年中，癌症患者通过使用药物靶向策略取得了重要的临床获益。然而，耐药性仍然是大多数癌症治疗中的一个主要问题。上皮-间充质可塑性（EMP）和肿瘤微环境已被描述为许多癌症类型中有效治疗的限制因素。此外，上皮-间充质转化（EMT）也与许多不同的临床前模型中的治疗耐药性有关，尽管从临床研究和临床样本中获得的证据有限。在这篇综述中，我们特别深入探讨了中间上皮/间充质（E/M）状态的机制及其与微环境的相互作用如何影响治疗耐药性。我们还描述了生物信息学和药物基因组学的应用将如何帮助确定 EMT 对药物耐药性的生物学影响，并为未来开发新的药理学方法。
