The efficacy of chemotherapeutic drug combinations may be predicted by concordance of gene response to the single agents

Gravett,Andrew M.; Dennis,Jayne L.; Dalgleish,Angus G.; Copier,John; Liu,Wai M.

doi:10.3892/ol.2020.12184

The efficacy of chemotherapeutic drug combinations may be predicted by concordance of gene response to the single agents

Authors:
- Andrew M. Gravett
- Jayne L. Dennis
- Angus G. Dalgleish
- John Copier
- Wai M. Liu
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Affiliations: Institute for Infection and Immunity, Department of Oncology, St. George's, University of London, London SW17 0RE, UK
Published online on: October 1, 2020 https://doi.org/10.3892/ol.2020.12184
Article Number: 321
Copyright: © Gravett et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Determining the expression of genes in response to different classes of chemotherapeutic drugs may allow for a better understanding as to which may be used effectively in combination. In the present study, the human colorectal cancer cell line HCT116 was cultured with equi‑active concentrations of a series of anti‑cancer agents. Gene expression profiles were then measured by whole‑genome microarray. Although each drug induced a unique signature of gene expression in tumour cells, there were marked similarities between certain drugs, even in those from different classes. For example, the antimalarial agent artesunate and the platinum‑containing alkylating agent, oxaliplatin, produced a very similar mRNA expression pattern in HCT116 cells with ~14,000 genes being affected by the two drugs in the same way. Furthermore, the overall correlation of gene responses between two agents could predict whether their use in combination would lead to a greater or lesser effect on cell number, determined experimentally, than predicted by single agent experiments. The results indicated that even when working through different mechanisms, combining drugs that initiate a similar transcriptional response may constitute the best option for determining drug‑combination strategies for the treatment of cancer.

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