Curative cancer therapy remains a major challenge particularly in cancers displaying multidrug resistance (MDR). The MDR phenotype is characterized by cross-resistance to a wide array of anticancer drugs harboring distinct structures and mechanisms of action. The multiple factors involved in mediating MDR may include host factors, tumor factors as well as tumor-host interactions. Among the host factors are genetic variants and drug-drug interactions. The plethora of tumor factors involves decreased drug uptake primarily via impaired influx transporters, increased drug efflux predominantly due to the overexpression of MDR efflux transporters of the ATP-binding cassette superfamily or due to drug efflux mediated by extracellular vesicles (EVs) or drug-loaded lysosomes undergoing exocytosis, deregulation of cell death mechanisms (i.e. anti-apoptotic modalities), enhanced DNA damage repair, epigenetic alterations and/or deregulation of microRNAs. The intratumor heterogeneity and dynamics, along with cancer stem cell plasticity, are important tumor factors. Among the tumor-host interactions are the role of the tumor microenvironment, selective pressure of various stressor conditions and agents, acidic pH and the intracellular transfer of traits mediated by EVs. The involvement of these diverse factors in MDR, highlights the need for precision medicine and real-time personalized treatments of individual cancer patients. In this review, written by a group of researchers from COST Action STRATAGEM “New diagnostic and therapeutic tools against multidrug resistant tumors”, we aim to bring together these multidisciplinary and interdisciplinary features of MDR cancers. Importantly, it is becoming increasingly clear that deciphering the molecular mechanisms underlying anticancer drug resistance, will pave the way towards the development of novel precision medicine treatment modalities that are able to surmount distinct and well-defined mechanisms of anticancer drug resistance.

治愈性癌症治疗仍然是一项重大挑战，特别是在显示多药耐药性（MDR）的癌症中。MDR表型的特征是对具有不同结构和作用机制的多种抗癌药物具有交叉耐药性。介导MDR的多种因素可能包括宿主因素，肿瘤因素以及肿瘤与宿主的相互作用。宿主因素包括遗传变异和药物相互作用。过多的肿瘤因素主要是通过受损的内流转运蛋白引起的药物吸收减少，药物外排增加，这主要是由于ATP结合盒超家族的MDR外排转运蛋白的过表达，或者是由于细胞外囊泡（EVs）或药物载量介导的药物外排溶酶体经历胞吐作用，细胞死亡机制失控（即 抗凋亡方式），增强的DNA损伤修复，表观遗传学改变和/或microRNA的失调。肿瘤内异质性和动力学以及癌症干细胞可塑性是重要的肿瘤因素。肿瘤与宿主之间的相互作用包括肿瘤微环境的作用，各种应激条件和作用剂的选择性压力，酸性pH值以及电动汽车介导的性状在细胞内的转移。这些不同因素在耐多药治疗中的参与突显了对个体癌症患者的精准医学和实时个性化治疗的需求。在这篇由COST Action STRATAGEM的研究人员撰写的文章中，“针对多药耐药性肿瘤的新型诊断和治疗工具”，我们旨在汇集MDR癌症的这些多学科和跨学科的特征。重要的，