Department of Mathematics and Statistics, University of Montreal, Montreal, Quebec H3C 3J7, Canada.
Sainte-Justine University Hospital Research Centre, Montreal, Quebec H3S 2G4, Canada.
Chem Rev. 2021 Mar 24;121(6):3352-3389. doi: 10.1021/acs.chemrev.0c00356. Epub 2020 Nov 5.
Drug resistance has profoundly limited the success of cancer treatment, driving relapse, metastasis, and mortality. Nearly all anticancer drugs and even novel immunotherapies, which recalibrate the immune system for tumor recognition and destruction, have succumbed to resistance development. Engineers have emerged across mechanical, physical, chemical, mathematical, and biological disciplines to address the challenge of drug resistance using a combination of interdisciplinary tools and skill sets. This review explores the developing, complex, and under-recognized role of engineering in medicine to address the multitude of challenges in cancer drug resistance. Looking through the "lens" of intrinsic, extrinsic, and drug-induced resistance (also referred to as "tolerance"), we will discuss three specific areas where active innovation is driving novel treatment paradigms: (1) nanotechnology, which has revolutionized drug delivery in desmoplastic tissues, harnessing physiochemical characteristics to destroy tumors through photothermal therapy and rationally designed nanostructures to circumvent cancer immunotherapy failures, (2) bioengineered tumor models, which have benefitted from microfluidics and mechanical engineering, creating a paradigm shift in physiologically relevant environments to predict clinical refractoriness and enabling platforms for screening drug combinations to thwart resistance at the individual patient level, and (3) computational and mathematical modeling, which blends in silico simulations with molecular and evolutionary principles to map mutational patterns and model interactions between cells that promote resistance. On the basis that engineering in medicine has resulted in discoveries in resistance biology and successfully translated to clinical strategies that improve outcomes, we suggest the proliferation of multidisciplinary science that embraces engineering.
耐药性极大地限制了癌症治疗的成功，导致癌症复发、转移和死亡。几乎所有的抗癌药物，甚至是新型免疫疗法，这些疗法都重新调整了免疫系统，以识别和破坏肿瘤，但都屈服于耐药性的发展。工程师们已经从机械、物理、化学、数学和生物等多个学科涌现出来，利用跨学科的工具和技能组合来应对耐药性的挑战。这篇综述探讨了工程学在医学中不断发展、复杂且未被充分认识的作用，以应对癌症耐药性的诸多挑战。通过“内在、外在和药物诱导的耐药性（也称为‘耐受性’）”的视角，我们将讨论三个正在积极创新以推动新治疗模式的特定领域：（1）纳米技术，它彻底改变了在纤维组织中药物的输送，利用物理化学特性通过光热疗法破坏肿瘤，并通过合理设计的纳米结构来规避癌症免疫疗法的失败，（2）生物工程肿瘤模型，得益于微流控和机械工程，在更接近生理的环境中实现了范式转变，以预测临床抵抗，并为筛选药物组合提供了平台，以阻止个体患者水平的耐药性，以及（3）计算和数学建模，它将计算机模拟与分子和进化原理相结合，以绘制突变模式并模拟促进耐药性的细胞之间的相互作用。基于工程学在耐药性生物学方面的发现以及成功转化为改善治疗效果的临床策略，我们建议多学科科学的蓬勃发展，应包含工程学。
