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

Morgan Craig, Adrianne L. Jenner, Bumseok Namgung, Luke P. Lee, Aaron Goldman

Research output: Contribution to journalReview articlepeer-review

40 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3352-3389
Number of pages38
JournalChemical Reviews
Volume121
Issue number6
DOIs
StatePublished - 24 Mar 2021

Bibliographical note

Funding Information:
A.G. was funded by a Breast Cancer Alliance Young Investigator Award. M.C. was funded by a Natural Science and Engineering Research Council (NSERC) of Canada Discovery Award RGPIN-2018-04546. A.J. was funded by a Fonds de recherche du Québec–Santé International Postdoctoral Fellowship, Centre for Applied Mathematics in Biosciences and Medicine (CAMBAM), and NSERC Discovery Award RGPIN-2018-04546. Images used for schematics were obtained from Servier.com .

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