Extending the Lymphoblastoid Cell Line Model for Drug Combination Pharmacogenomics

Abstract

Combination drug therapies have become an integral part of precision oncology, and while evidence of clinical effectiveness continues to grow, the underlying mechanisms supporting synergy are poorly understood. Immortalized human lymphoblastoid cell lines (LCLs) have been proven as a particularly useful, scalable and low-cost model in pharmacogenetics research, and are suitable for elucidating the molecular mechanisms of synergistic combination therapies. In this review, we cover the advantages of LCLs in synergy pharmacogenomics and consider recent studies providing initial evidence of the utility of LCLs in synergy research. We also discuss several opportunities for LCL-based systems to address gaps in the research through the expansion of testing regimens, assessment of new drug classes and higher-order combinations, and utilization of integrated omics technologies.

Keywords: :

• combination treatment
• drug response
• LCLs
• omics
• synergism

Author contributions

All authors contributed to the writing of the manuscript.

Acknowledgments

The authors would like to thank T Wiltshire, H McLeod and B Small for discussion on synergy in the LCL model.

Financial & competing interests disclosure

This work was supported by R01CA161608 from the National Cancer Institute and by intramural funds from the National Institute of Environmental Health Sciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by R01CA161608 from the National Cancer Institute and by intramural funds from the National Institute of Environmental Health Sciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.