Key Dates

NOT-CA-23-085 - Notice of Intent to Publish a Funding Opportunity Announcement for Pre-Cancer Atlas (PCA) Research Centers (U01 Clinical Trial Not Allowed)

National Cancer Institute (NCI)

The National Cancer Institute (NCI) intends to promote a renewed initiative by publishing a Notice of Funding Opportunity (NOFO) to solicit applications for Human Tumor Atlas (HTA) Research Centers, one of the three scientific components of the Human Tumor Atlas Network (HTAN) (NCI Human Tumor Atlas Network). HTAN is a collaborative research initiative and a community resource generating program that is tasked with generating spatial atlases of cancer transitions for a diverse set of precancers and advanced cancers that build upon the current set of public HTAN atlases. HTAN research will span across pivotal points in tumor evolution that include progression from premalignancy to malignancy, primary tumor to metastasis, locoregional tumor recurrence, and response and resistance to treatment. These atlases will enable the development of new classifiers and risk prediction tools, identification of potential targets for preventive interceptions, enhancement of diagnostic and treatment strategies for advanced cancers, and generation of compelling hypotheses to facilitate future research on underlying biological mechanisms. It is imperative that the HTAN atlases are clinically useful for the diverse populations in the United States and the construction process must be mindful of this important aspect.

The NOFO will utilize the U01 (Research Project - Cooperative Agreements; Clinical Trial Not Allowed) activity code. Each HTA Research Center will construct one human precancer or advanced cancer atlas describing one or more transitions spanning the entire cancer continuum: precancer to locally invasive cancer to metastatic cancer, locoregional recurrence, dynamic response to therapy, and development of therapeutic resistance. The atlas efforts must leverage and expand upon the current HTAN resources and infrastructure and focus on creating spatial atlases at single-cell resolution that are driven by specific topics in cancer biology. Research Centers will collaborate with other PCA and HTA Research Centers and the HTAN Data Coordinating Center (DCC). Research Centers will work with the DCC to make the data and analytical tools available to the research community.

This Notice is being provided to allow potential applicants sufficient time to develop a responsive HTA application. The NOFO is expected to be published in late summer 2023 with an anticipated application due date in fall 2023. Details of the planned NOFO are provided below and details of the planned pre-application webinar will be announced after publication of the NOFO.

This Notice encourages investigators with expertise and insights into this area of SPATIAL TUMOR ATLAS CONSTRUCTION to begin to consider applying for this new NOFO. In addition, collaborative investigations combining expertise in CLINICAL ONCOLOGY OR CANCER PREVENTION, TECHNOLOGY, BIOENGINEERING, DATA SCIENCE, SYSTEMS BIOLOGY AND/OR COMPUTATIONAL MODELING will be encouraged, and these investigators should also begin considering applying for this application. Among the areas of research encouraged in this initiative are TUMOR ATLASES THAT DESCRIBE THE MOLECULAR, CELLULAR, AND TISSUE-LEVEL SPATIAL RELATIONSHIPS OF CELLULAR AND NON-CELLULAR COMPONENTS OF THE TUMOR ECOSYSTEM DURING TUMOR INITIATION, PROGRESSION, METASTASIS, LOCOREGIONAL RECURRENCE, AND/OR RESPONSE AND RESISTANCE TO THERAPY and examining the mechanisms that underlie TUMOR EVOLUTION, as well as research designed to improve the translation of existing knowledge of strategies for the prevention and treatment of CANCER.

Each HTA Research Center will have three major areas of responsibility: (1) biospecimen acquisition, processing, and annotation, (2) molecular, cellular, and spatial characterization, and (3) data processing, analysis, modeling, and visualization. The objective of each HTA Research Center will be to construct no more than one tumor atlas that describes the molecular, cellular, and tissue-level spatial, functional, and/or temporal relationships of cellular and non-cellular components of the tumor ecosystem.

Multimodal mapping requirement: HTA Research Centers must include multimodal technological platforms for molecular, cellular and tissue characterization of selected biospecimens.

Spatial mapping requirement: HTA Research Centers should aim to quantify the 3D characteristics of tumor evolution. Atlases derived from technologies that ensure maximum information preservation within the 3D tumor microenvironment are desired.

Dynamic mapping requirement: Atlases must include detailed clinical data matched to patient biospecimens to guide analysis of the spatially reconstructed molecular, cellular, or tissue dynamic phenotypes that predict tumor initiation, progression, metastasis, local recurrence, and/or response and resistance to therapy. Tumor atlases supported under this FOA must focus on one of the following transitions in cancer:

• The transition from non-malignant to malignant disease, including, but not limited to, atlases characterizing precancer or carcinoma in situ lesions and matched recurrent non-malignant lesions and advanced cancers from the same patients, and precancers and other atypical lesions found in surgically resected specimens or rapid autopsy specimens in association with invasive cancers.
• The transition from locally invasive to metastatic cancer, including, but not limited to, atlases characterizing multiple metastatic sites, atlases describing the transition into or out of tumor dormancy, atlases capturing colonization of early disseminated tumor cells at distant sites.
• The dynamic response to therapy, including, but not limited to, atlases describing a positive response to traditional, targeted and/or immunotherapies, atlases that describe no response, incomplete response, or negative response to traditional, targeted and/or immuno-therapies.
• The development of therapeutic resistance, including atlases describing the transition from responsive to traditional, targeted, and/or immuno-therapy to resistant to that therapy.
• The recurrence of disease within the same patient including, but not limited to, atlases characterizing locally recurrent invasive cancer following treatment of the primary incidence.

Addressing Cancer Health Disparities

All HTAN atlases should contain a diversity of patient populations consistent with the requirements of the NIH Inclusion Policies for Research Involving Human Subjects (as described in https://grants.nih.gov/policy/inclusion.htm). It is imperative that the atlases include samples from patients whose self-identified racial and ethnic communities are expected to have genetic ancestries currently underrepresented in cancer research, underserved populations, or populations who experience disparate cancer outcomes. In case of cancers with known health disparities (i.e., triple negative breast cancer, prostate cancer, bladder cancer, etc.), patients from the affected population must be overrepresented within the sample collection plan. In all cases, applicants are strongly encouraged to, at a minimum, mirror the demographic distribution reported by the U.S. Census Bureau and there must be an adequate breadth of samples included within each Center so that future translational research based on the HTAN atlases are beneficial to the diverse US population.

Atlas use case requirement: The proposed atlas should generate testable hypotheses based upon a specific and timely use case that is clearly defined within the application.

The cancer type for atlas construction is not prescribed, but atlases that add significant value to the current set of HTAN atlases (www.humantumoratlas.org) will be prioritized. Significant value may be added through multiple approaches, including but not limited to, proposing tumor or tissue types not included in the first phase of HTAN, proposing to include a unique sample set that diversifies or extends the impact of an atlas constructed in the first phase of HTAN, and/or adding longitudinal samples that increase the insight and impact of atlases constructed during the first phase of HTAN.

More details will be outlined in the forthcoming NOFO.

Funding Information

Applications are not being solicited at this time.

Inquiries

Please direct all inquiries to:

Sharmi Ghosh-Janjigian, Ph.D.
Division of Cancer Biology
National Cancer Institute (NCI)
Telephone: 240-276-7122
Email: ghoshjanjigias@mail.nih.gov

Shannon Hughes, Ph.D.
Division of Cancer Biology
National Cancer Institute (NCI)
Telephone: 240-276-6224
Email: shannon.hughes@nih.gov