The complexity of cancer biology and its clinical manifestation are driven by genetic, epigenetic, transcriptomic, proteomic and metabolomic alterations, supported by genomic instability as well as by environmental conditions and lifestyle factors. Although novel therapeutic modalities are being introduced, efficacious cancer therapy is not achieved due to the frequent emergence of distinct mechanisms of multidrug resistance (MDR). Advanced technologies with the potential to identify and characterize cancer MDR could aid in selecting the most efficacious therapeutic regimens and prevent inappropriate treatments of cancer patients. Herein, we aim to present technological tools that will enhance our ability to surmount drug resistance in cancer in the upcoming decade. Some of these tools are already in practice such as next-generation sequencing. Identification of genes and different types of RNAs contributing to the MDR phenotype, as well as their molecular targets, are of paramount importance for the development of new therapeutic strategies aimed to enhance drug response in resistant tumors. Other techniques known for many decades are in the process of adaptation and improvement to study cancer cells’ characteristics and biological behavior including atomic force microscopy (AFM) and live-cell imaging. AFM can monitor in real-time single molecules or molecular complexes as well as structural alterations occurring in cancer cells induced upon treatment with various antitumor agents. Cell tracking methodologies and software tools recently progressed towards quantitative analysis of the spatio-temporal dynamics of heterogeneous cancer cell populations and enabled direct monitoring of cells and their descendants in 3D cultures. Besides, novel 3D systems with the advanced mimicking of the in vivo tumor microenvironment are applicable to study different cancer biology phenotypes, particularly drug-resistant and aggressive ones. They are also suitable for investigating new anticancer treatment modalities. The ultimate goal of using phenotype-driven 3D cultures for the investigation of patient biopsies as the most appropriate in vivo mimicking model, can be achieved in the near future.

遗传，表观遗传学，转录组学，蛋白质组学和代谢组学改变，以及基因组不稳定性以及环境条件和生活方式因素，都推动了癌症生物学的复杂性及其临床表现。尽管正在引入新的治疗方法，但是由于多种药物耐药性（MDR）独特机制的频繁出现，仍未实现有效的癌症治疗。具有识别和表征癌症的潜力的先进技术MDR可以帮助选择最有效的治疗方案，并防止对癌症患者进行不适当的治疗。在此，我们旨在介绍一些技术工具，这些工具将在未来十年内增强我们克服癌症耐药性的能力。其中一些工具已经在实践中，例如下一代测序。鉴定导致MDR表型的基因和不同类型的RNA及其分子靶标对于开发旨在增强耐药性肿瘤药物反应的新治疗策略至关重要。数十年来已知的其他技术正在适应和改进过程中，以研究癌细胞的特征和生物学行为，包括原子力显微镜（AFM）和活细胞成像。AFM可以实时监测单分子或分子复合物，以及在用各种抗肿瘤剂治疗后在癌细胞中发生的结构改变。细胞追踪方法学和软件工具最近朝着定量分析异质癌细胞群体的时空动态发展，并使得能够直接监测3D培养物中的细胞及其后代。此外，新颖的3D系统具有先进的模拟功能，体内肿瘤微环境可用于研究不同的癌症生物学表型，特别是耐药性和侵袭性表型。它们也适用于研究新的抗癌治疗方式。使用表型驱动的3D培养物作为最合适的体内模拟模型来研究患者活检的最终目标可以在不久的将来实现。