Key Dates

August 21, 2023 - Notice of Intent to Publish a Funding Opportunity Announcement for Human Tumor Atlas (HTA) Research Centers (U01 Clinical Trial Not Allowed). See NOT-CA-23-086

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 Pre-Cancer Atlas (PCA) 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 PCA Research Center will construct one 3-D precancer atlas that comprehensively characterizes a pre-malignant lesion with an explicit focus on understanding the transition from a precancerous lesion to malignancy. 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 PCA application. The NOFO is expected to be published in September 2023 with an anticipated application due date in December 2023. Details of the planned pre-application webinar will be announced in the Guide 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 atlases that utilize spatial, temporal and omics data in conjunction with multimodal patient data to characterize precancerous lesions as they progress to invasive cancer, regress, or obtain a state of equilibrium. A precancer atlas is a comprehensive, dynamic, high-resolution, multidimensional, multiparametric, temporal and scalable atlas of precancerous lesions and their surrounding microenvironment for select organ sites, including cancers that disproportionally affect minority, underserved, and high-risk populations or high-risk precancerous lesions or state with known genetic, hereditary, and inflammation background would be of great interest. The data will be interrogated to characterize precancerous lesions and understand the subsequent events that drive the transition from a premalignant lesion to a malignant cancer as a function of time, find molecular markers of risk and early detection, identify targets to intercept and prevent development of invasive cancer and for predictive modeling to chart the potential trajectories of tumor development and progression.

The objective of each PCA Research Center is to construct one multimodal, dynamic, and spatial atlas of a precancerous lesion by conducting comprehensive molecular, cellular, and tissue characterization of a human precancerous lesion and its microenvironment with spatial resolution. PCA Research Centers should focus on deriving insights from the most informative measures, that could be bulk or single cell molecular analysis and should develop at least one complete atlas with potential clinical significance. Applicants must propose to collect at least two existing HTAN data types (HTAN data standards; data access) for which data and metadata standards and levels exist (at least one must be a spatial assay) to accelerate data sharing and integrative analysis. When possible, the Centers must include longitudinally collected specimens from the same patients where outcome can be evaluated. These atlases should provide a deeper understanding of the transition of precancerous lesions to invasive cancer, generate testable hypotheses and have the potential to identify markers for early detection and risk assessment and molecular targets for preventive intervention.

Research conducted by PCA Research Center may include, but is not limited to:

• Determining the dynamics of somatic mutations; the interaction of germline mutations with somatic mutations, copy number alterations or other molecular changes that affect cellular fitness and immunity and contribute to initiation and progression of precancer lesions to frank malignancy, or regression.
• Leveraging recent developments in high-content molecular analyses (including single-cell and bulk analysis) to determine spatial and temporal dynamics (longitudinal measurements) of precancerous lesions and the surrounding microenvironment in detection of genomic drivers of progression or regression.
• Detecting spatial, functional and/or temporal features that are based on clinical context and allow for the development of methods (biomarkers) for cancer risk assessment or early detection and/or for the identification of targets for prevention of invasive cancers.

Rationale for selection of organ site should include following:

• Impact on Public Health: The proposed atlas should have the potential to have a substantial impact on clinical decision-making as well as its use by the scientific community. This is determined by public health burden, prevalence of the tumor, nature of the clinical question to be addressed, health disparities in racially and ethnically diverse populations, high risk populations and care settings.
• Access to Technologies and Biospecimens: The applicants must have access to state-of-the-art technologies and the resources to obtain well-characterized and well-annotated biospecimens (cross-sectional and longitudinal). Collected samples must be of high quality, quantity (for use in a variety of assays) and purity. While the final atlas-building effort should use uniformly collected and extensively annotated, longitudinal biospecimens, applicants are encouraged to apply HTAN developed and standardized technologies to interrogate retrospective samples (https:\\www.humantumoratlas.org).
• Feasibility of Atlas Construction: The feasibility of atlas construction is based on the available cohorts, number of available biospecimens, rate of progression to cancer and available tools and technologies.
• Synergistic Partnerships for Maximizing Resources: The ability to partner with ongoing initiatives (federal, foundation, industry, etc.) is vital as this will increase access to cohorts, technologies, and other resources necessary for atlas construction. In this context, applicants are encouraged to collaborate with major programs under the Division of Cancer Prevention  including Cancer Prevention-Interception Targeted Agent Discovery Program (CAP-IT), Cancer Preclinical Drug Development Program (PREVENT), Early Detection Research Network (EDRN), Translational and Basic Science Research in Early Lesions (TBEL) Program, Cancer Prevention Clinical Trials Network (CP-CTNet) and NCI Community Oncology Research Program (NCORP). 

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. 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  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:

Sudhir Srivastava, PhD, MPH
Division of Cancer Prevention (DCP)
National Cancer Institute (NCI)
Telephone: 240-276-7028
Email: sudhir.srivastava@nih.gov

Nicholas Hodges, PhD
Division of Cancer Prevention (DCP)
National Cancer Institute (NCI)
Telephone: 240-309-8155
Email: nick.hodges@nih.gov

Indu Kohaar, PhD
Division of Cancer Prevention (DCP)
National Cancer Institute (NCI)
Telephone: 240-620-0875
Email: indu.kohaar@nih.gov