OCG supports The Cancer Target Discovery and Development (CTD2) initiative, a collaborative network of 13 different research teams, or Centers. The program strives to functionally validate discoveries from large-scale genomic initiatives and advance them toward precision medicine through the efforts of the Centers and open access data sharing.
Large-scale initiatives, such as The Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and Cancer Genome Characterization Initiative (CGCI) are systematically cataloging molecular alterations of many tumor types. These efforts have shed light on the underlying causes of certain cancer subtypes. However, challenges remain in translating molecular information into patient-based treatment strategies. For example:
- Mining and managing the enormous datasets generated by genomics initiatives are difficult for researchers without bioinformatics expertise.
- Cancer genomes are inherently unstable. They often have large numbers of genetic and epigenetic alterations, the majority of which do not likely contribute to tumor etiology. Distinguishing the alterations that actually drive tumor initiation, progression, and/or maintenance is, therefore, challenging.
- Alterations in some common oncogenes and tumor suppressors, such as RAS and TP53, respectively, have not been easy to target therapeutically.
The CTD2 Network was born from the need to address these challenges and build on the fundamental findings generated from genomic initiatives. Through robust cross-Network collaborations, CTD2 uses innovative bioinformatics, functional biology, high-throughput small molecule, genetic screens, and protein-protein interactions and to: (1) mine data to find alterations that potentially influence tumor biology, (2) characterize the functional roles of candidate alterations in cancers, and (3) identify novel approaches that target causative alterations either directly or indirectly.
Figure: The CTD2 Network has evolved over the past several years. The Network initiated with a Pilot phase, which included five participating Centers. It has since expanded to include more Centers. Read about the Network and its mission in the inaugural publication Towards patient-based cancer therapeutics.
Each of the 13 Centers that comprise CTD2 contributes unique yet complementary expertise. Approaches include bioinformatics, genome-wide loss-of-function in vitro and ex vivo screening, small molecule high-throughput screening, and protein-protein interactions, among others. Project descriptions, datasets, and methodologies generated by the Centers are shared through the CTD2 Data Portal. Analyzed data, experimental observations, and other positive results from the Centers’ efforts are compiled in the CTD2 Dashboard. Because CTD2 is a “community resource project,” all information in the Data Portal and Dashboard is openly available to the scientific community and can be accessed without restrictions. Through these mechanisms, any investigator can utilize and expand upon the Network’s insights and tools.
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 development of clinically useful markers, targets, and therapeutics for precision medicine.