Cell panel screening assays are essential in modern drug discovery. However, traditional short-term assays often fail to adequately capture the response profiles of slow-acting therapeutics, particularly those targeting epigenetic pathways. To fully realize the potential of these drug candidates, it is crucial to optimize the assay conditions for extended periods as long-term assays.
High-throughput cell panel screening enables researchers to efficiently evaluate potential therapeutic agents across a range of cancer cell lines. This method quickly identifies conditions that impact cellular processes, such as proliferation and growth inhibition, while also uncovering mechanisms of sensitivity and resistance. These screenings provide essential insights for drug selection, patient stratification, drug repurposing, and investigations into the mechanism of action.
Cell panel screening and epigenetics
Standard cell panel screening typically lasts 3-6 days, which is sufficient for most agents. However, this duration often lacks the resolution necessary to fully characterize compounds that act more slowly and target epigenetic pathways.
There is mounting evidence that epigenetic changes play a significant role in the development and progression of cancer. Alterations in DNA methylation can silence tumor suppressor genes. At the same time, modifications to histones can change genome accessibility and gene expression patterns, potentially leading to oncogenesis. Furthermore, these epigenetic mechanisms contribute to treatment resistance, making therapeutic interventions more challenging. As a result, epigenetics is becoming a key area for identifying new therapeutic targets and is a priority in cancer research. This evolution highlights the need for advanced tools to evaluate compounds that target epigenetic pathways.
An advanced long-term assay platform
Our preclinical services team has developed an advanced long-term assay platform to analyze cell line sensitivity to slow-acting therapeutics, such as epigenetic modulators. This specialized cell panel screening lasts for 10 days, revealing prolonged treatment effects across various cancer cell lines.
All assays require high cell quality and standardized seeding protocols for reproducibility, which are especially critical for long-term applications. Extended assays necessitate thorough optimization to maintain resolution during prolonged culture periods. Our approach utilizes optimized, reduced seeding densities, which eliminate the need for cell splitting or media replenishment during the 10 days, thereby minimizing experimental interference. Additionally, our long-term assays are designed with specific controls to reduce variability associated with low seeding densities to provide more reliable results.
The data obtained offers valuable insights into the mechanisms of drug candidates and highlights potential therapeutic targets. However, identifying which specific families of epigenetic enzymes or classes of compounds are most significantly enhanced by extended assays remains an ongoing area of research. This highlights the need for strategic decision-making when choosing between traditional 6-day screening methods and extended time-point screening approaches.
Summary
Our OncoSignature™ 2D Long-Term Assay is part of a comprehensive suite of cell-based assays supporting the drug discovery pipeline, complementing our services capabilities in cell line engineering, functional genomics, and immuno-oncology.
Find out more about how our preclinical services and OncoSignature 2D long-term assay platform can help advance your drug discovery research.
For research use only. Not for use in diagnostic procedures.
