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

Martin Michaelis,Jindrich Cinatl,Mark N Wass

doi:10.20517/cdr.2019.005

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.

Highlights

Despite improvements in therapy outcomes in recent decades, except for a few exceptions cure rates remain low for www.cdrjournal.comMichaelis et al
Since many models will be needed to cover the complexity associated with acquired resistance formation, we have established the Resistant Cancer Cell Line collection by adapting initially chemosensitive cancer cell lines to clinical concentrations of targeted and cytotoxic anti-cancer drugs to enable the systematic investigation of acquired drug resistance mechanisms
The DEN50-R platform is another project dedicated to the generation of drug-adapted cancer cell line panels. This perspective is focused on the use of drug-adapted cancer cell lines as models of acquired drug resistance in cancer

Summary

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 www.cdrjournal.comMichaelis et al. DRUG-ADAPTED CANCER CELL LINES REFLECT CLINICAL RESISTANCE MECHANISMS They have enabled the discovery of major drug resistance mechanisms and the identification and elucidation of clinically relevant acquired resistance mechanisms to targeted and cytotoxic anti-cancer drugs[33].

Results

Conclusion