Type

Journal Article

Authors

Britta Stordal
Norma O'Donovan
Martin Clynes
John Crown
Laura Breen
Steven Busschots
Alex J Eustace
Martina McDermott

Subjects

Pharmacology

Topics
drug therapy drug development breast cancer case studies drug resistance cell therapy cancer chemotherapy cancer cell lines

In vitro Development of Chemotherapy and Targeted Therapy Drug-Resistant Cancer Cell Lines: A Practical Guide with Case Studies. (2013)

Abstract The development of a drug-resistant cell line can take from 3 to 18 months. However, little is published on the methodology of this development process. This article will discuss key decisions to be made prior to starting resistant cell line development; the choice of parent cell line, dose of selecting agent, treatment interval, and optimizing the dose of drug for the parent cell line. Clinically relevant drug-resistant cell lines are developed by mimicking the conditions cancer patients experience during chemotherapy and cell lines display between two- and eight-fold resistance compared to their parental cell line. Doses of drug administered are low, and a pulsed treatment strategy is often used where the cells recover in drug-free media. High-level laboratory models are developed with the aim of understanding potential mechanisms of resistance to chemotherapy agents. Doses of drug are higher and escalated over time. It is common to have difficulty developing stable clinically relevant drug-resistant cell lines. A comparative selection strategy of multiple cell lines or multiple chemotherapeutic agents mitigates this risk and gives insight into which agents or type of cell line develops resistance easily. Successful selection strategies from our research are presented. Pulsed-selection produced platinum or taxane-resistant large cell lung cancer (H1299 and H460) and temozolomide-resistant melanoma (Malme-3M and HT144) cell lines. Continuous selection produced a lapatinib-resistant breast cancer cell line (HCC1954). Techniques for maintaining drug-resistant cell lines are outlined including; maintaining cells with chemotherapy, pulse treating with chemotherapy, or returning to master drug-resistant stocks. The heterogeneity of drug-resistant models produced from the same parent cell line with the same chemotherapy agent is explored with reference to P-glycoprotein. Heterogeneity in drug-resistant cell lines reflects the heterogeneity that can occur in clinical drug resistance.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

Britta Stordal, Norma O'Donovan, Martin Clynes, John Crown, Laura Breen, Steven Busschots, Alex J Eustace, Martina McDermott

Experts in our system

1
Britta Kristina Stordal
Trinity College Dublin
Total Publications: 28
 
2
Norma O'Donovan
Dublin City University
Total Publications: 52
 
3
Martin Clynes
Dublin City University
Total Publications: 209
 
4
John Crown
Dublin City University
 
5
Laura Breen
Dublin City University
Total Publications: 11
 
6
Steven Busschots
Trinity College Dublin
Total Publications: 7
 
7
Alex J Eustace
Royal College of Surgeons in Ireland
Total Publications: 23
 
8
Martina McDermott
Dublin City University
Total Publications: 7