The current standard of care for many aggressive diseases, such as cancer and HIV, depends on drug combinations. For example, certain chemotherapy regimens used for the treatment of blood cancers can include up to five or more drugs. Historically, these regimens were established through a lengthy, trial-and-error clinical process.
With an increasing number of approved and investigational drugs, the discovery of novel drug combinations through clinical trial-and-error is not feasible. To address this inefficiency, NCATS’ Chemistry Technology team uses matrix combination screening. This platform enables NCATS scientists to quickly narrow down a long list of potential drug combinations and find those with the most potential to help patients.
The NCATS’ matrix combination screening platform can rapidly test the effect of different drug combinations on cellular, molecular or biochemical processes that are relevant to a disease of interest. The Chemistry Technology team screens the best pairs to find the optimal concentration of each drug and learn more about their effect on cells, such as whether that combination is toxic. Scientists can use the results of these screens to pursue testing of promising drug combinations in animals and, ultimately, humans.
The Matrix Combination Screening Platform
The state-of-the-art, qualitative, high-throughput matrix combination screening platform relies on a highly integrated robotics system, custom data analysis software and a unique Web-interface that provides straightforward and intuitive data browsing.
Thousands of combination-pairs can be analyzed with this platform in a robust, cost and time-effective way, enabling NCATS scientists to quickly narrow down a long list of drug-pairs to identify the most-effective drug combinations for follow-up and clinical studies.
The unbiased discovery of drug combinations through the matrix platform may yield treatments with increased effectiveness; delayed onset of resistance and deliverable at lower, less toxic doses. As of December 2017, NCATS scientists have initiated two clinical trials and several preclinical studies based on the findings from this platform.
Top: Heat map representing activities of different drug combinations from a compound library activity derived from an assay determined through quantitative high-throughput matrix screening. The colors indicate different responses (i.e., inhibitory or activation response), and color intensity represents potency. Bottom left: Examples of two compounds by name and chemical structure from the NCATS compound collection. Bottom right: An example of a 10×10 dose-response matrix block experiment.)
Matrix Screening Projects
NCATS scientists work on a variety of matrix combination screening projects. Learn more about NCATS’ active projects.
