CTD2: Bridging Genomics to Therapeutics
, by Subhashini Jagu, Ph.D. & Freddie L. Pruitt, Ph.D.
Cancer is a genetic disease. Large-scale national and international cancer profiling studies, such as The Cancer Genome Atlas Project (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Cancer Genome Characterization Initiative (CGCI) have generated an anthology of multi-scale –“omics” data spanning mutations, gene expression, epigenetics and proteomic data. The staggering level of genome complexity and ever expanding wealth of information produced by cancer genomic sequencing efforts has made it difficult for the research community to process the findings and prioritize the most meaningful therapeutic options for patients.
CTD2 Established to Bridge Gap Between Genomics and Precision Oncology
The Cancer Target Discovery and Development (CTD2) initiative was established by the National Cancer Institute (NCI) to bridge the gap between cancer genomics and precision oncology by mining large-scale genomic datasets for alterations important in cancer etiology and translating the discoveries into effective treatments. The goal of the Network was to develop novel bioinformatics and functional genomics approaches to identify therapeutic targets, perturbagens that affect the targets, and biomarkers, thereby impeding survival of the cancer cells. Importantly,
- The Data Portal provides access to all raw and analyzed data generated by CTD2 Centers.
- The Dashboard compiles experimental observations and other positive results from CTD2 efforts.
- As a “community resource project,” all CTD2 Data Portal and Dashboard information are openly available to the scientific community and can be accessed without restrictions.
CTD2 Enables Functional Research and Clinical Trials
The initial phase of CTD2 Network Centers generated 19 novel bioinformatic tools which enable the identification of therapeutic targets, gene and molecular networks, driver mutations, and chemical sensitivities. These tools are available to the scientific community and can be accessed through the CTD2analytical tools page.
The Network also generated reagents including CRISPR libraries, reagents to study protein-protein interactions, and cDNA clones with cancer relevant mutations, are made available to the research community. These reagents foster growth of genomics and precision medicine science and can be found through the CTD2supported reagents page.
The Network has been highly successful and published over 260 manuscripts with preclinical and clinical relevance. The results from some studies have provided supporting evidence for the initiation of several clinical trials, including the following drug and cancer combinations:
- Ruxolitinib and Trastuzumab in metastatic HER2 positive breast cancer (NCT02066532)
- ACY-1215 and Nab-paclitaxel in metastatic breast cancer (NCT02632071)
- MK-1775, Docetaxel, and Cisplatin in head and neck cancer (NCT02508246)
- Selinexor and Docetaxel in KRAS mutant non-small cell lung cancer (NCT03095612)
New Phase of CTD2 Focuses on Therapeutic Resistance
The newly approved CTD2 Network will explore cancer complexity in terms of inter-patient and intra-tumor heterogeneities and their impacts (i.e., on innate or acquired resistance to chemo and immunotherapies) and develop efficient strategies (combinatorial approaches) to overcome treatment resistance. This phase was approved by the Board of Scientific Advisors because of the accomplishments (some of which are highlighted above) and collaborative nature of the Network to address the lessons learned from the previous phase. The new Network Centers cover multiple specialties, including:
- genome-wide loss-of-function in vitro and ex vivo screening
- small molecule high-throughput screening
- protein-protein interactions
- patient-derived cancer models developed from the Human Cancer Models Initiative (HCMI) for high-throughput functional studies to define biologically relevant targets, modulators, and biomarkers
Through active collaboration and the sharing of data and resources with the cancer research community, CTD2 will contribute to understanding the mechanisms of cancer and potentially accelerate the development of clinically useful markers, targets, and therapeutics for precision oncology.
To find out more about CTD2 and other programs supported by the Office of Cancer Genomics, visit ocg.cancer.gov.