Despite the large investment in biomarker discovery and validation, few major early detection cancer biomarkers have been approved for clinical use over the last 25 years. In addition, many initially promising biomarkers have not been validated. One issue is that biomarker discovery and validation has typically occurred in studies that were initially designed with different a priori hypotheses in mind. Such studies may not be appropriate for studies of biomarker validation or detection.
To accurately discover and validate cancer biomarkers, researchers need access to resources where serial collections (i.e., collecting specimens from the same person at different points in time), epidemiological and clinical data, and outcomes were assessed over time and specimen handling procedures are well documented. Serial blood samples (including plasma or serum) collected in a systematic and equivalent manner before the diagnosis of cancer occurred with appropriate epidemiological and clinical annotation are ideal for discovery and/or validation of biomarkers for early detection. Few empirical examples exist in which high-quality, well annotated specimens have been utilized to assess early detection biomarker validity, and new collections are typically expensive and time-consuming to establish.
Recognizing these challenges, National Cancer Institute (NCI) staff from the Epidemiology and Genomics Research Program (EGRP) and Division of Cancer Prevention consulted with extramural researchers to discuss the possibilities for aggressively leveraging existing clinical and epidemiology cohort resources. These discussions generated a great deal of excitement and preliminary data, and a workshop was planned in order to further explore these possibilities. As a prelude to the workshop, a commentary presenting the challenges and ideas to be discussed in the meeting was published in Cancer Epidemiology, Biomarkers and Prevention.
On August 28-29, 2013, the NCI held the “Utilizing Existing Biospecimen Resources from Epidemiological Studies and Clinical Practice for Discovery or Validation of Markers for Early Cancer Detection” Workshop. In brief, some of the fundamental issues identified by participants were whether the study designs or conditions (including biospecimen collection, storage, and sharing considerations) necessary for an unbiased study of biomarkers could be grafted onto existing cohorts, including HMOs and other clinical cohorts. The three main recommendations from the meeting are to:
- Understand the current inventory of specimens and data available for researchers,
- Engage stakeholders to share innovative solutions for the issue at hand, and
- Establish pilot studies to demonstrate how existing resources or infrastructures can be used to answer specific questions about diagnostic discrimination of biomarkers.
NCI is currently working on the first two recommendations, and is seeking input from others for how to proceed with the third recommendation. An NCI-wide inventory of biospecimens and data in NCI-funded extramural studies is being developed to help investigators assess the suitability of existing data/specimens for future studies. In order to further engage epidemiologists, laboratory scientists, and bioinformaticians in further discussion of the issues raised during the August 2013 workshop, NCI is sponsoring a session at the 2014 AACR Annual Meeting focused on how existing studies and HMO infrastructures may be leveraged for unbiased research into biomarker study and validation for early detection.
What Do You Think?
EGRP invites you to share your ideas for potential pilot studies that would demonstrate how existing infrastructures/resources can be used for biomarker discovery and validation for early detection of cancer. If you have questions that could be addressed by feasibility or demonstration studies (or reasons why those questions are important), please comment in the space below.
Additionally, EGRP has identified several potential sources of biospecimens for investigators on our Biospecimen Resources for Population Scientists web page. If you are aware of other relevant resources that are not listed on our webpage, please let us know, and we will consider including them in the future.
Danielle Mercatante Carrick, Ph.D., M.H.S. is a Program Director in the EGRP Host Susceptibility Factors Branch (HSFB). She manages a research grant portfolio related to genetic and immunologic factors that influence personal susceptibility to cancer.
Sheri Schully, Ph.D. is Team Lead for the Knowledge Integration Team in EGRP’s Office of the Associate Director. Dr. Schully’s responsibilities include systematically managing the accumulating knowledge base and tools for cancer epidemiology and genomics to accelerate research, evidence-based recommendations, and translation into prevention and clinical practice. In addition, she manages a portfolio of grants related to factors that influence personal susceptibility to cancer, such as genetic and hormonal factors.