NCATS experts use a technology called matrix combination screening to quickly narrow down a long list of potential drug combinations and find those with the most potential to help patients. The matrix screening approach uses NCATS’ robotic, high-throughput screening platform to quickly conduct millions of tests to assess the effects of a combination of therapeutic compounds on cellular, molecular or biochemical processes that are relevant to a disease of interest. Read the latest news about these activities below.
NCATS Collaborations Lead to Potential New Drug Combinations for Childhood Cancers
To help address the challenges in treating children with cancer, a team of researchers in NCATS’ Chemistry Technology and Matrix Screening programs is rethinking treatment approaches for several difficult-to-treat childhood cancers.
Matrix Screen Identifies Synergistic Combination of PARP Inhibitors and Nicotinamide Phosphoribosyltransferase (NAMPT) Inhibitors in Ewing Sarcoma
Ewing’s sarcoma is a pediatric cancer with limited treatment options. Drug screening identified that the combination of two small molecules, Daporinad and Niraparib, is highly effective in killing Ewing’s sarcoma cells. The group found that Daporinad’s inhibition of a metabolic enzyme increases the effectiveness of Niraparib, resulting in cancer cell death.
PAX3–FOXO1 Establishes Myogenic Super Enhancers and Confers BET Bromodomain Vulnerability
Rhabdomyosarcoma, a pediatric cancer, is frequently caused by a mutation in a transcription factor altering gene expression, leading to unregulated cell growth. This study focuses on how this mutation affects DNA structure and gene regulation. It found a protein, BRD4, that is critical for cell survival. Screening of BRD4 inhibitors demonstrated that cells with the mutation are highly sensitive to these compounds.
Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma
This is a proof-of-concept study validating that the Bruton’s tyrosine kinase inhibitor, Ibrutinib, enhances the efficacy of chemotherapy against Primary CNS lymphoma.
mQC: A Heuristic Quality-Control Metric for High-Throughput Drug Combination Screening
This study introduces a predictive, interpretable quality control metric for evaluation of high-throughput combination screening results.
A Druggable TCF4 and BRD4-Dependent Transcriptional Network Sustains Malignancy in Blastic Plasmacytoid Dendritic Cell Neoplasm
A combination of RNAi and high-throughput small molecule screening identified a cellular transcription factor that regulates the oncogenic program of an aggressive and largely incurable hematologic cancer, identifying small molecule inhibitors for clinical evaluation.
Chemical Screens Identify Drugs That Enhance or Mitigate Cellular Responses to Antibody-Toxin Fusion Proteins
A team from NCATS and the National Cancer Institute investigate the interaction between small molecule and antibody-based therapeutics. The goal of this approach would be to enhance the anticancer activity of the antibody-based therapeutic, which possess high specificity to the cancer cells, while limiting systemic toxicity.
Cancer network activity associated with therapeutic response and synergism
Researchers at NCATS demonstrate that cancer therapeutic responses can be predicted on the basis of a systems-level analysis of molecular interactions and gene expression.
Data Released on Drug Combinations to Treat Malaria
A team of researchers from NCATS and the National Institute of Allergy and Infectious Diseases screened and released data on thousands of combinations of known and newly identified drugs to potentially treat malaria. This work highlights a number of potentially novel antimalarial combinations for drug-development.
Screening Platform Is a Launch Pad for Novel Treatment Combinations
NCATS and National Cancer Institute investigators published a collaborative study that demonstrated how a new combination drug screening platform developed at NCATS can quickly narrow down a long list of potential drug combinations to find those with the most potential to help patients.