Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) will support the program "Cancer Target Discovery and Development” (CTD2, pronounced cee-tee-dee-squared). CTD2 is focused on efforts that advance cancer research by bridging the knowledge gap between the large volumes of comprehensive molecular characterizations of many cancer types and studies of the underlying etiology of cancer development, progression, and/or metastasis.
The primary purpose of CTD2 is to advance the following areas:
- Improving the understanding of how mutations in cancer-associated genes affect the protein activity (e.g., gain-of-function, loss-of-function, or neomorphic function) within the cellular pathway(s) they are part of and the cellular changes that result within the context of various tumors and the microenvironment;
- Identifying new molecular targets with the goal to understand their wiring mechanisms and how to overcome innate and/or acquired resistance to therapies, particularly clinical resistance related to inter- and intra- tumor heterogeneity; and
- Developing efficient strategies to identify appropriate multiple targets and optimal combination of perturbagens (chemical or biological; immunotherapeutics being a prime example of the latter) with the potential to eliminate all cancer cells, despite their clonal heterogeneity and their surrounding microenvironment.
This FOA solicits applications for U01 cooperative agreement research projects addressing the areas outlined above. The proposed projects should use a combination of state-of-the-art high throughput informatic and experimental approaches to: characterize and validate novel cancer targets; develop precise perturbagens that can affect the proposed targets of cancer treatments and define the mechanism(s) of action; identify molecular markers that can meaningfully predict responses or resistance to anticancer therapies and develop algorithms that can be applied to predict responses to treatments and/or define more precise treatment modalities.