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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Opinion Article

Experimental Determination of Cancer Drug Targets with Independent Mechanisms of Resistance

Author(s): Abigail R. Bland, Nensi Shrestha, Maddie Berry, Christabel Wilson and John C. Ashton*

Volume 22, Issue 2, 2022

Published on: 08 March, 2022

Page: [97 - 107] Pages: 11

DOI: 10.2174/1568009622666220107152014

Price: $65

Abstract

Mathematical modelling of tumour mutation dynamics has suggested that cancer drug targets that have different resistance mechanisms should be good candidates for combination treatment. This is because the development of mutations that cause resistance to all drugs at once should arise relatively infrequently. However, it is difficult to identify drug targets fulfilling this requirement for particular cancers. Here we present four experimental criteria that we argue are necessary (but not sufficient) conditions that drug combinations should meet in order to be considered for combination drug treatment aimed at delaying or overcoming cancer drug resistance. We present the results of our own experiments - guided by these criteria - using anaplastic lymphoma kinase mutated lung cancer cells. Each set of experiments demonstrate results for different drug combinations. We conclude that the combination of ALK and MEK inhibitors come closest to meeting all our criteria.

Keywords: ALK, drug resistance, combination treatment, lung cancer, mathematical modelling, drug targets.

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