Oss, February, 22nd, 2018 –Compound profiling in cell line panels is a powerful tool in the development of new cancer medicines. Analysis of drug sensitivity across cell lines can reveal response biomarkers in the form of specific genetic mutations or the expression of cancer genes. These response biomarkers can guide subsequent in vivo experiments, and, ultimately, the selection of patients most likely to respond to new drugs in clinical trials. NTRC has set up a panel of 102 cancer cell lines, known as Oncolines™, which enables drug sensitivity analyses and biomarker discovery. The Oncolines™ panel yields highly reproducible data and captures drug response through various metrics [1].

The correct quantification of drug response in cell proliferation assays is the subject of active scientific study. It has been suggested, for instance, that growth rate differences between cell lines may influence IC50 values. To address this, Hafner et al. [2] recently proposed a Growth Rate (GR) metric which quantifies the effect of a drug on growth rate, relative to the growth rate of the untreated cell line. This metric corrects for differences in growth, seeding density and assay time frame, which may confound the comparison of IC50 values. The GR score ranges from 1 (full growth rate) to 0 (cytostasis) to -1 (full growth inhibition) (Figure 1).

To give our users access to this new development, NTRC now includes GR50 and GRmax as optional response metrics in its Oncolines™ 102 cell lines platform, in addition to the regular reporting of IC50, GI50 and LD50 values. Oncolines™ GR50 data can also be used to search for drug response biomarkers via pharmacogenomic analysis. According to Hafner et al. this may lead to biomarkers that are better translatable to in vivo situations [2].

Figure 1. Example of dose-response curves with GR scoring.

Literature references

[1] Uitdehaag et al. (2015) Molecular Cancer Therapeutics 15, 3097-3109.
[2] Hafner et al. (2016) Nature Methods 13, 521-527.

About NTRC

NTRC is a precision medicine company dedicated to the development of new anti-cancer drugs. NTRC facilitates the development of novel therapies by providing cancer cell line profiling services (Oncolines™, OncolinesProfiler™, GeneNominator™, SynergyFinder™ and SynergyScreen™) and target residence time measurements for protein kinases (ResidenceTimer™) on a fee-for-service basis. NFK GreenScreen™, an assay read-out for the cancer immunotherapy drug targets IDO1 and TDO, is supplied to clients globally. NTRC has internal drug discovery programs on TTK, IDO1 and TDO. For more information please visit www.ntrc.nl or contact [email protected]