Anti-cancer strategies may include targeting enzymes that modulate chromatin, known as epigenetic modulators. To meet the challenge of testing candidates for epigenetic approaches, our Eurofins Discovery experts developed OncoPanel® human cancer cell models for testing in long-term culture assays.
Our long-term (up to 10-day) cell proliferation, viability, and multiplex assays for epigenetic and other slow-acting therapeutics are key because they allow sufficient time for observation of biological effects and to ensure the potential for epigenetic modulation by a test agent is captured.
All assay formats are available from Eurofins Discovery across a broad sampling of genetically diverse human cancer cell lines covering a wide range of cancer subtypes. Turnaround time for focused panels of 1 – 30 cell lines is 35 business days, depending upon study scope; larger and full panel studies run approximately 60-75 business days, depending upon study start date.
Key quality benefits
- Validated cell lines obtained from reliable repositories
- Culture conditions are optimized to ensure logarithmic growth during extended culture and assay periods
- Reliable and reproducible data
Long-term culture assays, as with all OncoPanel Services, provide insights on clinical potential in human cell-based assays prior to clinical trials. Benefits include:
- Prioritize test agents for further evaluation
- Benchmark test agents to standards-of-care
- Identify biomarkers for prediction of treatment response or potential resistance
- Applicable for combination studies, assessed in a 9×9 matrix format
As an example below, the EZH2-selective inhibitors GSK343 and UNC1999 elicit responses dependent on both extended assay duration and EZH2 mutational status, whereas other less targeted inhibitors, such as the pan-kinase inhibitor staurosporine, show little or no preference for either condition. Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase enzyme that participates in histone methylation and, ultimately, transcriptional repression.
Detection of growth inhibition by EZH2 inhibitors requires an extended assay duration
Figure 1. A. Representative data from 3- and 10-day cell growth assays measuring the activity of distinct EZH2 inhibitors in the Pfeiffer (EZH2 mutant) cell line. B. Sensitivity of EZH2 mutant cell lines to the EZH2 inhibitor, GSK343, is increased with increased exposure time, whereas the non-specific kinase inhibitor, staurosporine, shows no preference for EZH2 mutational status or assay duration. C. Histone methylation is shown as an overlay with standard OncoPanel data to demonstrate effects on proliferation (cell count) and apoptosis induction. Such mechanistic markers can be included in OncoPanel studies as potential custom, add-on features.
