Details

Autor(en) / Beteiligte

• Kimble, Danielle C.
• Dvergsten, Erik
• Thomeas-McEwing, Vasiliki
• Karovic, Sanja
• Conrads, Thomas P.
• Maitland, Michael L.

Titel

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

Ist Teil von

• Gynecologic oncology, 2021-01, Vol.160 (1), p.295-301

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 IC20, IC50, and IC80 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, 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. 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. •PharmacoDB comprises extensive data on drugs and cancer cell lines including for ovarian and uterine cancer.•Although a broadly useful resource, the reproduction of individual experiment results has been limited.•The coverage of drugs widely used to treat ovarian and uterine cancers is incomplete.•The computed results of some exposure-response relationships were strikingly reproducible in the lab.•Invalid results usually emerged from original high-throughput experiments with incomplete ranges of drug concentrations.