Department of Biological Sciences & the Bioinformatics Research Center, NC State University, Raleigh, NC, USA.
Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA.
Pharmacogenomics. 2021 Jun;22(9):543-551. doi: 10.2217/pgs-2020-0160. Epub 2021 May 28.
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.
联合药物治疗已成为精准肿瘤学的一个组成部分，虽然临床疗效的证据不断增加，但支持协同作用的潜在机制仍知之甚少。永生化人淋巴母细胞系 (LCL) 已被证明是药物遗传学研究中一种特别有用、可扩展且低成本的模型，非常适合阐明协同联合治疗的分子机制。在这篇综述中，我们介绍了 LCL 在协同药物基因组学中的优势，并考虑了最近提供 LCL 在协同研究中应用初步证据的研究。我们还讨论了基于 LCL 的系统通过扩展测试方案、评估新的药物类别和更高阶的组合以及利用综合组学技术来解决研究空白的几种机会。
