Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Commun Biol. 2024 Sep 7;7(1):1101. doi: 10.1038/s42003-024-06812-3.
In pre-clinical trials of anti-cancer drugs, cell lines are utilized as a model for patient tumor samples to understand the response of drugs. However, in vitro culture of cell lines, in general, alters the biology of the cell lines and likely gives rise to systematic differences from the tumor samples' genomic profiles; hence the drug response of cell lines may deviate from actual patients' drug response. In this study, we computed a similarity score for the selection of cell lines depicting the close and far resemblance to patient tumor samples in twenty-two different cancer types at genetic, genomic, and epigenetic levels integrating multi-omics datasets. We also considered the presence of immune cells in tumor samples and cancer-related biological pathways in this score which aids personalized medicine research in cancer. We showed that based on these similarity scores, cell lines were able to recapitulate the drug response of patient tumor samples for several FDA-approved cancer drugs in multiple cancer types. Based on these scores, several of the high-rank cell lines were shown to have a close likeness to the corresponding tumor type in previously reported in vitro experiments.
在抗癌药物的临床前试验中，细胞系被用作患者肿瘤样本的模型，以了解药物的反应。然而，细胞系的体外培养通常会改变细胞系的生物学特性，并可能导致与肿瘤样本基因组图谱的系统差异；因此，细胞系的药物反应可能与实际患者的药物反应不同。在这项研究中，我们计算了一个相似性得分，用于选择在遗传、基因组和表观遗传水平上与二十两种不同癌症类型的患者肿瘤样本具有密切和遥远相似性的细胞系，整合了多组学数据集。我们还考虑了肿瘤样本中免疫细胞的存在和癌症相关的生物学途径在这个评分中的作用，这有助于癌症的个性化医学研究。我们表明，基于这些相似性得分，细胞系能够再现多种癌症类型中几种已批准用于临床的抗癌药物的患者肿瘤样本的药物反应。基于这些得分，一些高排名的细胞系在之前报道的体外实验中显示出与相应肿瘤类型的密切相似性。
