Inova Schar Cancer Institute, Inova Health System, 8081 Innovation Park Drive, Fairfax, VA 22031, USA.
Women's Health Integrated Research Center, Women's Service Line, Inova Health System, 3300 Gallows Road, Falls Church, VA 22042, USA.
Gynecol Oncol. 2021 Jan;160(1):295-301. doi: 10.1016/j.ygyno.2020.10.044. Epub 2020 Nov 13.
Publicly available data on drug sensitivity for cancer cell lines have been curated into a single, integrated database, PharmacoDB. The contributing datasets report modeled estimates of drug effect from high throughput assays. These databases have been informative for developing new broad insights, but the reliability of these data specifically for drugs used to treat ovarian and uterine cancers in related cell lines has not been reported.
In vitro viability assays were performed on A2780, OVCAR-3, TOV-21G, and RL95-2 cells with nine drugs to produce high resolution exposure-response curves. Lab generated data were compared to publicly available datasets by IC, IC, and IC values, and the area between the logarithmic logistic regression curves.
For exposure-response curve comparisons with clinically indicated drugs between lab generated and publicly available data, the majority had area-between-curves less than 20%, indicating similarity. However, 15 out of 40 of these dataset curves were incomplete as indicated by the lack of, or extrapolated, IC value. The common ovarian and uterine cancer drug, carboplatin, exemplified this incomplete status as all of the available dataset curves were incomplete and therefore non-informative.
For gynecologic malignancy cell line models, experimental drug sensitivity data is comparable to the available data in PharmacoDB when exposure-response curves are complete. Incomplete exposure-response curves due to incomplete concentration ranges tested and related extrapolation of IC values can mislead individual drug/cell line pair data for downstream applications.
已将癌症细胞系药物敏感性的公开可用数据整理到一个单一的综合数据库 PharmacoDB 中。这些贡献数据集报告了来自高通量测定的药物作用的模拟估计值。这些数据库对于开发新的广泛见解很有帮助，但尚未报告这些数据对于用于治疗卵巢和子宫癌的相关细胞系中的药物的可靠性。
在 A2780、OVCAR-3、TOV-21G 和 RL95-2 细胞中进行了九种药物的体外活力测定，以产生高分辨率的暴露-反应曲线。通过 IC、IC 和 IC 值以及对数逻辑回归曲线之间的面积，将实验室生成的数据与公开可用数据集进行比较。
对于实验室生成和公开可用数据之间具有临床意义的药物的暴露-反应曲线比较，大多数曲线之间的面积小于 20%，表明相似性。然而，这些数据集曲线中有 15 个是不完整的，表明缺乏或推断的 IC 值。常见的卵巢和子宫癌药物卡铂就是这种不完整状态的例子，因为所有可用的数据集曲线都是不完整的，因此没有信息。
对于妇科恶性肿瘤细胞系模型，当暴露-反应曲线完整时，实验药物敏感性数据与 PharmacoDB 中的可用数据具有可比性。由于测试的浓度范围不完整以及相关的 IC 值外推，导致暴露-反应曲线不完整，可能会误导下游应用的个别药物/细胞系对数据。
