Functional Genomics Research
Cells with genes highlighted by florescent dyes grow in multi-well plates.
Functional genomics research examines the role of the genome in cancer. By testing hypotheses derived from structural genomics research, or by generating new ideas from experiments in cancer cells, functional genomics research reveals patterns in cancer biology that can sometimes be directly translated to precision cancer care. Studies like those from The Cancer Target Discovery and Development (CTD2) Network, have already discovered genomic vulnerabilities in cancer that can be exploited through targeted treatments. Many of CCG’s functional genomics experiments further investigate insights from structural genomics studies, which are carried out by CCG’s Genome Characterization Pipeline.
Key Questions
- How do altered genes in cancer work together within pathways to promote abnormal proliferation and survival?
- Can molecular pathways affected by genetic abnormalities in cancer genes be targeted with available drugs or new compounds?
- Can tumor models generated from patient biopsies be used to understand mechanisms of therapeutic efficacy or resistance?
Tools and Methods
CCG’s functional genomics studies use models of cancer for high-throughput drug screens, gene perturbation experiments using RNA interference and CRISPR-Cas9 technology, and many other genome-wide techniques. Currently, CCG researchers use cancer cell lines, tumor organoid cultures that grow in petri dishes, or mice bearing grafts from human tumors to determine the effects of particular genetic alterations. Recognizing the power of new methods for generating cancer models, CCG is supporting the development of cutting-edge organoid and conditionally reprogrammed cell models to promote the safe and effective translation of functional cancer genomics findings to clinical care.
Programs and Collaborations
Cancer Target Discovery and Development (CTD2) Network
The CTD2 Network bridges a major gap between cancer genomics and precision oncology by mining large-scale genomic datasets for alterations important in cancer development and translating those discoveries into treatment. The CTD² Network emphasizes collaborations between the funded Centers, which have expertise in various computational and functional genomic approaches. In addition to publishing novel results, the CTD2 Network produces publicly available data, analytical tools, and reagents.
All data generated are open-access and can be obtained from the websites listed below:
- Raw and analyzed primary data are available through the CTD2 Data Portal
- Network-generated observations and results, with associated supporting evidence, are compiled in a web interface known as the CTD2 Dashboard
Human Cancer Models Initiative (HCMI)
HCMI is an international collaboration between the NCI, Cancer Research UK, the Wellcome Trust Sanger Institute, and the foundation Hubrecht Organoid Technology with the goal of generating a publicly available bank of 1,000 next-generation cancer models annotated with genomic and clinical data.
HCMI uses new, innovative technologies, including organoid and conditionally reprogrammed cell (CRC) culturing techniques, to create cancer models that more accurately represent the architecture and complexity of real tumors. The models also have associated genomic data and clinical data made available to the research community.
NCI is contributing to this international consortium by providing funding and support to two Cancer Model Development Centers (CMDCs), which will develop a subset of the HCMI's next-generation cancer models from patient tissues.
Next-Generation Technologies (NGT)
Next-Generation Technologies supports the development of technology tools to facilitate and accelerate research using next-generation cancer models, such as organoids and conditionally reprogrammed cells. The tools will focus on utilizing models developed by NCI's Human Cancer Models Initiative. Protocols, materials, and knowledge developed by the program will be shared broadly and expeditiously with the research community.