Evaluation of publicly available in vitro drug sensitivity models for ovarian and uterine cancer

医学 卡铂 药品 子宫癌 卵巢癌 逻辑回归 曲线下面积 癌症 计算生物学 肿瘤科 药理学 内科学 生物 化疗 顺铂
作者
Danielle C. Kimble,Erik Dvergsten,Vasiliki Thomeas-McEwing,Sanja Karovic,Thomas P. Conrads,Michael L. Maitland
出处
期刊:Gynecologic Oncology [Elsevier]
卷期号:160 (1): 295-301
标识
DOI:10.1016/j.ygyno.2020.10.044
摘要

Objective 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. Methods 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 IC20, IC50, and IC80 values, and the area between the logarithmic logistic regression curves. Results 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, IC50 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. Conclusions 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.
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