Aims & Objectives

• Foster a community of scientists, clinicians, researchers and patient advocates with a shared common interest in precancers and developing novel interception approaches.
• Facilitate and conduct cross-cutting research that enables a more targeted approach in determining the relationship between cancer hallmarks, precancer initiation, and potential interception prior to invasive disease progression.
• Create opportunities to translate this knowledge into actionable clinic utility.
• Understand genomic alterations and biologic pathways which characterize increased risk of progression to invasive cancer in patients with precancer.
• Determine those patients who will not progress to invasive disease/save them from unnecessary surgical treatment.

Identifying the processes by which precancerous cells progress to invasive disease and understanding their mode of action are pivotal in designing intervention strategies at the earliest possible time point that possess the maximum clinical utility [1]. The Pre-cancer Research for Early Lesion Understanding, Diagnosis, and Evaluation (PRELUDE) Study aims to provide insights into a crucial aspect of cancer initiation by discovering novel drivers of cancer progression from precancer to invasive disease and identifying precancer that is harmful from indolent precancer.

A key PRELUDE approach will be to compile multi-dimensional and multi-scale information on precancers to facilitate the construction of genomic risk classifiers across a range of disease-specific areas. These classifiers will perform risk stratification to identify precancers that may progress to invasive disease. Future application of biomarker sets may be translated into more informed, value-concordant care for patients and stakeholders affected by precancers across a variety of disease-specific areas. It may chart a path to implementation of a biomarker-driven, individualized treatment paradigm that enables the safe de-escalation of surgery for some patients; it will also allow identification of high-risk cohorts of precancer patients. The utility of a biomarker-based personalized risk stratification tool will be of immense clinical utility both in identification of precancer patients at greatest risk for developing invasive disease, as well as for discovery of new targets for precancer prevention strategies.

Molecular and cellular characterization of precancers may also assist with pretreatment counseling, inform clinical trial development (i.e. window of opportunity studies and other trials), and identify other therapeutic targets of interest. Subsequent correlative science studies identified by the PRELUDE WG stand to improve future precancer pathology diagnostics, prognostics and care management. Results from PRELUDE will be translated into population health benefit by appropriate data integration and sharing with the global precancer research community ​across​ ​multiple​ ​platforms so that additional analyses can be conducted. These discoveries will serve as the basis for future precision targeting of pathways that are of specific relevance for precancer populations for prevention and treatment. This will enable new research directions for the next generation of genomic and molecular studies to be developed that may continue to transform precancer treatment and prevention options in the future. In sum, the work of PRELUDE will facilitate the development of research and technology that can impact treatment decisions for individuals diagnosed with precancer and ensure the translation of research findings into everyday clinical practice.

[1] Stangis MM, Chen Z, Min J, et al. The Hallmarks of Precancer. Cancer Discov. 2024 April 04; 14(4): 683–689. doi:10.1158/2159-8290.CD-23-1550.

PRELUDE receives funding from DCI, the Cinelli Family Foundation and the John Wayne Cancer Foundation. We would like to acknowledge and thank our funders for their ongoing contribution and support.

A key aspect of PRELUDE is engagement with key stakeholder groups to take patient and caregiver needs fully into account and ensure our work is both meaningful and relevant. We will engage with representatives from patient advocacy groups across a variety of disease-specific areas and diverse populations to ensure precancer patient and caregiver perspectives are fully incorporated into all aspects of our work; this will include close collaboration with organizations that represent vulnerable and underserved populations to develop culturally sensitive strategies. All patient and stakeholder partners will have equal authority to present concerns and change strategies relating to all aspects of PRELUDE.

We will facilitate cross-cutting advocacy initiatives for shared learning where patients and caregivers across each disease-specific area will be enabled to describe barriers and challenges associated with the management of their specific precancer and their personal concerns related to it. Patient advocacy network platforms will be developed to provide meaningful, intentional, and bi-directional discussion about these potential barriers and challenges, with common themes, learnings and potential solutions identified; the lived experience of precancer patients and caregivers from one disease-specific area may thus be utilized to inform patients/caregivers from a range of other different disease areas.

Biospecimen Repository

The PRELUDE team will have access to a large-scale, comprehensive, well-annotated biospecimen repository of breast, blood, and digital pathology samples from existing biobanks; this will include an extraordinary number of diverse, clinically annotated archival samples that currently exist as part of institutional blood and tissue repositories at Duke. A collaboration with the BioRepository and Precision Pathology Center(BRPC) will facilitate biospecimen collection and storage. The BRPC is a shared resource of the Duke Cancer Institute and the Duke School of Medicine and is housed in the Department of Pathology.

Data Repository and Statistical Hub

The PRELUDE team will also have access to a vast clinical data repository from Duke Health and extensive clinical trial and population-based datasets that span the continuum between precancer and invasive disease. Clinical data elements will be collected both retrospectively and prospectively for patients contributing blood, tissue and imaging. Data will be standardized following industry state-of-the-art practices, appropriately annotated and prepared for ingestion by analytic tools and approaches to multimodal data analysis.

Development of Risk Classifiers

A key aspect of PRELUDE will be to develop integrative classifiers incorporating molecular, cellular and epidemiological features to identify associations between risk factors and early oncogenic drivers, and develop a risk model for precancerous disease, thus informing future models of cancer initiation. The validation of these risk classifiers against biospecimens and images that implement a human-in-the-loop framework involving clinicians, pathologists, and biostatisticians may ensure clinical relevance and contextual insight.

Artificial Intelligence Research

AI initiatives, machine learning model development and integrative analytical techniques will further improve our ability to predict the future risk of precancers across multiple disease-specific areas. Research studies will utilize longitudinal AI models to construct a foundation for creating a dynamic and interpretable framework to assess the risk of a patient developing invasive cancer from a precancer.

Epidemiology/Population Health Research

The inclusion of epidemiologists and population health expertise will enable PRELUDE to highlight the importance of contextual factors in medical data, provide a unique vantage point from which to identify the interactions between tissue, host, and environment in the progression from precancerous tissue to invasive disease, and contribute to the determination of future public health policy in this area.

The goal of the PRELUDE Pilot Studies Program is to support early-stage precancer projects that explore novel hypotheses, generate preliminary data, and lay the groundwork for future extramural funding.

There will be two one-year awards granted in 2026 (both in the Spring cycle). The awards are intended to foster innovative, high-impact research that advances understanding of the fundamental mechanisms underlying precancer initiation, progression, and response to therapy. Each award will support a precancer research project with a distinct focus: infrastructure and feasibility/acceptability for a prospective cohort to assess precancer outcomes

The projects may be quantitative or qualitative (with a quantitative component) in nature, and projects that reflect community and/or patient perspectives and address the burden of precancer in our catchment area are strongly encouraged.

The initial project period may not exceed 12 months. The total direct costs for the entire project period may not exceed $50,000. Indirect costs are not allowed. A one-time no-cost extension (NCE) may be considered if project activities are not expected to be completed by the project end date and unexpended funds remain. Requests for a NCE must be submitted to no later than August 9, 2027 (Project End Date).

The PRELUDE Steering Committee will select, review and prioritize internal pilot project funding applications. Each application will be peer reviewed by two members of the Steering Committee, followed by a roundtable discussion and scoring of the most meritorious applications by the entire committee.

A competitive renewal process for additional funding may be accessed after Year 1 based on the presentation of satisfactory preliminary results. Funds may be budgeted for fellow stipends, research staff, community partners, community outreach and engagement activities, supplies, local travel, and other expenses required for the completion of the project. 

For questions about this funding opportunity, contact PRELUDE Administrator Thomas Lynch at thomas.lynch2@duke.edu