March 14, 2014: NCATS Technology Is Transforming the Search for Combination Drug Treatments

For many diseases, there is no single “magic bullet” therapy. Instead, combining two or more drugs is the standard of care for diseases such as cancer, tuberculosis and HIV/AIDS. Combinations of drugs can work better than a single therapy, providing patients with a more effective treatment while also making it more difficult for diseased cells and microbes to develop resistance. In 2013, the U.S. Food and Drug Administration released guidance for the co-development of investigational drugs used in combination, further encouraging advancement of this promising therapeutic strategy.

Still, a major problem remains: How can researchers best determine which drug combinations show enough promise to move forward into clinical trials? Almost all of the multidrug therapeutics used currently in the clinic resulted from years of trial and error. For example, a combination of drugs known as R-CHOP is the standard of care for several types of lymphoma, a cancer of the white blood cells. It took decades for clinicians to assemble this five-drug treatment, yet despite these efforts, it is an ineffective therapy for many people battling lymphoma. Unfortunately, this example is not an isolated one. As patients await new advances in treatment, and with limited research dollars, we have insufficient time and resources to continue developing combination therapies using the traditional iterative process.

Thanks to the work of NCATS biologists, chemists, engineers, informaticians and other experts, we now have an efficient way forward: a high-throughput technology platform for screening novel two-drug combinations in diseased cells. Because this system can quickly narrow down a long list of potential drug combinations to identify those with the most potential to help patients, it could shave years off the process of developing effective multidrug treatments.

To showcase this advance in light of the Center’s “3Ds”:

  • A multidisciplinary NCATS team first developed the screening system to address the obstacle of finding potential drug combinations quickly and efficiently.
  • To test the system, the team engaged partners throughout NIH, including clinical experts working on cancers and infectious diseases. The team, in collaboration with researchers from the National Cancer Institute, first publically demonstrated the power of the platform using a common, aggressive form of lymphoma.
  • When the study was complete, team members disseminated the data and the NCATS-designed software to the larger research community.

This is just one example of how NCATS works to overcome roadblocks that hinder the translation of a basic science discovery into a new health intervention. Along with other efforts, such as our RNAi screening and data-sharing initiatives that I highlighted in January, NCATS’ work is generating great interest in the broader translational research community. I’m thrilled to be able to share these examples of game-changing new approaches and technologies from NCATS scientists and collaborators.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences