NOT-CA-21-080 - Notice of Intent to Publish a Funding Opportunity Announcement for Cancer Prevention-Interception Targeted Agent Discovery Program (CAP-IT) Data and Resource Coordination Center (DRCC) (U24 Clinical Trial Not Allowed)
National Cancer Institute (NCI)
The purpose of this Notice is to announce the NCI's intention to issue a Funding Opportunity Announcement (FOA) as a Request for Applications (RFA) for Cancer Prevention-Interception Targeted Agent Discovery Program (CAP-IT) Centers (U54). The overall goal of this FOA and the companion FOA (see Notice of Intent to Publish, NOT-CA-21-080) is to establish an agile and effective network infrastructure that undertakes collaborative research to discover molecularly or immunologically targeted agents designed to prevent or intercept oncogenic process in high-risk populations for precision cancer prevention and interception.
In this FOA, cancer prevention means primary prevention of cancer before oncogenic process begins, while cancer interception is defined as disruption of oncogenic process during precancer stage. Precision cancer prevention-interception refers to an approach employing cancer preventive-interceptive interventions individually tailored for different populations with an increased risk of cancer (high-risk populations), such as those with hereditary cancer syndromes (HCS) and individuals diagnosed with high-grade precancerous lesions (precancer).
The CAP-IT program aims to functionally validate the critical roles of lead oncogenic targets (oncotargets) selected from previous or ongoing research studies and/or from existing databases of genomic and molecular profiles of precancer and cancer, and to discover innovative oncotarget-directed agents through in vitro and in vivo efficacy evaluation for precision cancer prevention-interception applications. The ultimate goals of the CAP-IT program are to advance newly discovered efficacious cancer preventive or interceptive agents to the existing preclinical development pipeline, PREVENT Program, for further development towards IND and early phase clinical trials conducted by Cancer Prevention Clinical Trials Network (CP-CTNet) and thereby establish a scientific roadmap and a more streamlined foundational infrastructure for fast-tracking agent discovery and development for cancer prevention and interception from bench to bedside.
Each CAP-IT Center created through this FOA shall have a consortium of multi-disciplinary laboratories that cooperatively function and support research to validate oncotargets through functional evaluation studies and then discover potentially efficacious agents that interact with these oncotargets for cancer prevention and interception.
This Notice is being provided to allow potential applicants sufficient time to develop a responsive, multicomponent CAP-IT application. The companion notice for the CAP-IT Data and Resource Coordination Center (CAP-IT DRCC; U24) is NOT-CA-21-080.
The FOA is expected to be published in Summer 2021 with an anticipated application due date in Fall 2021. Details of the planned pre-application webinar will be announced in the Guide after publication of the FOA.
The FOA will utilize the U54 (Specialized Center, Cooperative Agreements) activity code.
Details of the planned FOA are provided below.
Reduction in cancer mortality can be significantly improved if the full potential of effective cancer prevention-interception is realized through mitigation of cancer risk and better management of precancer, especially in individuals with HCS and those diagnosed with high-grade precancer, by harnessing the increasing knowledge of early drivers of oncogenic process. Because high-risk cohorts represent a diverse group of individuals with different genetic susceptibilities, varying histories of exposure to carcinogens, different lifestyles, age, gender, and the presence of other comorbidities, it is virtually impossible to find and deliver universally efficacious cancer preventive interventions in this heterogenous population. A more rational approach to cancer prevention and interception in the high-risk cohorts is to employ preventive measures specifically tailored for individual risk factors, an approach referred to as precision cancer prevention-interception in this FOA. Success of precision cancer prevention-interception clearly depends on two complementary steps. First, high-risk individuals need to be identified, e.g. through screening and early detection of precancer, some of which may progress to cancer, and testing for genetic susceptibility. Second, rather than (or in addition to) surgical resection or ablation, innovative, safe, and efficacious measures designed to reduce cancer risk or molecularly/immunologically intercept, arrest, and possibly eliminate precancer in these high-risk individuals are needed. However, current cancer interception strategies are predominantly centered on surgical interventions, as very few target-specific agents are available for these high-risk individuals. It is this gap in discovering and bringing molecular and immunological agents closer to the high-risk populations for cancer prevention and interception that the CAP-IT program will address.
Oncotargets selected for CAP-IT research include actionable targets and those deemed potentially exploitable for interventions. Actionable targets represent previously identified and validated targets as drivers or enhancers of oncogenesis, against which efficacious agents are already available, but have not been tested for cancer prevention and interception. These agents include FDA approved or clinically investigated agents developed for non-oncological indications. Potentially exploitable targets are those detected in tumor precursor cells or in tumor stroma, which consists of immune cells, fibroblasts and other stromal components, and are determined based on the extent of expression, cell-type specificity (e.g. precancerous cells, tumor stromal components, and normal cells), types (i.e. mutated vs. wild type proteins), cellular expression patterns, timing (e.g. expressed early in oncogenesis), and prevalence of target expression among a defined high-risk cohort.
The CAP-IT program’s overall research objectives are as follows:
1) To collaborate with NCI and other programs that have research focus on molecular profiling of precancer, early cancer, and/or oncogenic signaling pathways with emphasis on high-risk populations, and prioritize high-value oncotargets that can be potentially exploited for intervention
2) To functionally validate the critical roles of the high-value oncotargets in tumor initiation and/or progression to invasive cancer and select oncotargets suitable for targeted intervention strategies
3) To discover innovative intervention agents (molecular and immunological) through in vitro and in vivo efficacy evaluation and select promising efficacious agents for further preclinical development
The CAP-IT program network structure: To achieve the research objectives, the CAP-IT program network will be formed by up to three U54 Specialized Centers (CAP-IT Centers) and one U24 Data and Resource Coordination Center (CAP-IT DRCC) (NOT-CA-21-080) .
To maximize the potential of team science efforts, each CAP-IT Center (U54) shall combine/integrate capabilities from a multi-institutional/multi-laboratory arrangement aimed to undertake multi-disciplinary research with the following three major focus areas: target validation, agent screening, and in vivo efficacy testing. Each CAP-IT Center will be led by a lead principal investigator (PI) or multi-PI, who will be responsible for assembling and coordinating a team of expert lead investigators assigned to oversee each CAP-IT Center project.
The CAP-IT priority research project activities: In response to the FOA, each CAP-IT Center shall initially propose two (2) Research Projects that will directly address the CAP-IT program’s research objectives by carrying out research activities that may include, but are not limited to:
CAP-IT project investigators will establish a project-specific research framework, including research aims and strategies for a well-defined high-risk cohort (such as a well characterized HCS cohort), selection criteria for specific organ-sites for a given project, oncotarget prioritization criteria, and overall project workflow and collaborative coordination plans. In addition to the emerging PreCancer Atlas database, there are existing NCI programs with accessible molecular profiling and biomarker databases (e.g. EDRN, CPTAC, CTD2, MCL, GDC) as well as informatics algorithms, tools, and resources that are available from NCI-sponsored informatics initiatives, including NCI Informatics Technology for Cancer Research (ITCR). CAP-IT investigators will be able to start collaborating with these programs upon inception of the program.
Network-level collaboration(s) will be facilitated though steering committee activities, network-wide meetings, and coordination through the CAP-IT DRCC (U24) (NOT-CA-21-080). Technical and scientific exchange will be enabled through the Cooperative Agreement process.
More details will be outlined in the forthcoming FOA.
$3,600,000 per year for 5 years with additional $400,000 for administrative supplements from year 2 to year 4.
$1,200,000 total cost per U54
Applications are not being solicited at this time.
Please direct all inquiries to:
Shizuko Sei, M.D.
Division of Cancer Prevention
National Cancer Institute (NCI)