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Michaelis et al. Cancer Drug Resist 2019;2:447-56 Cancer
DOI: 10.20517/cdr.2019.005 Drug Resistance

Review Open Access

Drug-adapted cancer cell lines as preclinical models
of acquired resistance

Martin Michaelis , Mark N. Wass , Jindrich Cinatl jr. 2
1
1
1 School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
2 Institut für Medizinische Virologie, Klinikum der Goethe-Universität, Frankfurt am Main, Germany.
Correspondence to: Martin Michaelis, School of Biosciences, University of Kent, Canterbury CT2 7N, UK. E-mail: m.michaelis@
kent.ac.uk; Mark Wass, School of Biosciences, University of Kent, Canterbury CT2 7N, UK. E-mail: m.n.wass@kent.ac.uk;
Jindrich Cinatl jr., Institut für Medizinische Virologie, Klinikum der Goethe-Universität, Frankfurt am Main, Germany.
E-mail: cinatl@em.uni-frankfurt.de

How to cite this article: Michaelis M, Wass MN, Cinatl jr. J. Drug-adapted cancer cell lines as preclinical models of acquired
resistance. Cancer Drug Resist 2019;2:447-56. http://dx.doi.org/10.20517/cdr.2019.005

Received: 21 Jan 2019 First Decision: 26 Apr 2019 Revised: 17 May 2019 Accepted: 23 May 2019 Published: 19 Sep 2019
Science Editor: Godefridus J. Peters Copy Editor: Huan-Liang Wu Production Editor: Jing Yu

Abstract
Acquired resistance formation limits the efficacy of anti-cancer therapies. Acquired and intrinsic resistance differ
conceptually. Acquired resistance is the consequence of directed evolution, whereas intrinsic resistance depends
on the (stochastic) presence of pre-existing resistance mechanisms. Preclinical model systems are needed to study
acquired drug resistance because they enable: (1) in depth functional studies; (2) the investigation of non-standard
treatments for a certain disease condition (which is necessary to identify small groups of responders); and (3) the
comparison of multiple therapies in the same system. Hence, they complement data derived from clinical trials and
clinical specimens, including liquid biopsies. Many groups have successfully used drug-adapted cancer cell lines
to identify and elucidate clinically relevant resistance mechanisms to targeted and cytotoxic anti-cancer drugs.
Hence, we argue that drug-adapted cancer cell lines represent a preclinical model system in their own right that is
complementary to other preclinical model systems and clinical data.

Keywords: Cancer, acquired drug resistance, cancer cell lines, drug adaptation, cancer therapy, cancer models

INTRODUCTION
Despite improvements in therapy outcomes in recent decades, except for a few exceptions (e.g., testicular
cancer, Hodgkin’s lymphoma, childhood acute lymphoblastic leukaemia) cure rates remain low for

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
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