Engineering in Medicine To Address the Challenge of Cancer Drug Resistance: From Micro- and Nanotechnologies to Computational and Mathematical Modeling,Chemical Reviews

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Engineering in Medicine To Address the Challenge of Cancer Drug Resistance: From Micro- and Nanotechnologies to Computational and Mathematical Modeling
Chemical Reviews ( IF 51.4 ) Pub Date : 2020-11-05 , DOI: 10.1021/acs.chemrev.0c00356
Morgan Craig _{1,

2} , Adrianne L Jenner _{1,

2} , Bumseok Namgung _{3,

4} , Luke P Lee _{3,

4} , Aaron Goldman _{3,

4}

Affiliation

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.

中文翻译：

应对癌症耐药性挑战的医学工程：从微型和纳米技术到计算和数学建模

耐药性极大地限制了癌症治疗的成功，导致复发、转移和死亡率。几乎所有抗癌药物，甚至是重新校准免疫系统以识别和破坏肿瘤的新型免疫疗法，都已屈服于耐药性的发展。机械、物理、化学、数学和生物学科出现了工程师，他们使用跨学科工具和技能组合来应对耐药性挑战。本综述探讨了医学工程在解决癌症耐药性方面的众多挑战方面的发展、复杂和未被充分认识的作用。透过内在、外在和药物诱导的耐药性（也称为“耐受性”）的“镜头”，它将计算机模拟与分子和进化原理相结合，以绘制促进抵抗的细胞之间的突变模式和模型相互作用。基于医学工程已经导致耐药生物学的发现并成功转化为改善结果的临床策略，我们建议包含工程的多学科科学的扩散。

更新日期：2020-11-05

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