The DoD Omics Consortium to Study the Origins of Ovarian Cancer (DOCSOOC)
Abstract
Scientific Objective and Rationale: The objective of this Consortium Development application is to establish a consortium infrastructure through new and existing relationships between four institutions with outstanding scientists, clinicians, and ovarian cancer consumer advocates. The consortium will perform a preliminary research project to determine the role of the local cellular environment during the transition from normal tissue, to precursor lesion, and to invasive cancer using multiple scientific approaches to probe multiple aspects of the cancer genome. We have made substantial progress in identifying the likely precursor lesions for ovarian cancers. Most advanced-stage, high-grade serous ovarian cancers originate in the fallopian tube, and less aggressive endometrioid and clear cell ovarian cancers develop from pre-existing pelvic endometriosis. However, delineating how these precursor lesions develop into cancer and subsequently spread is an important unmet need that will lead to improvements in prevention and early detection of ovarian cancer. Consortium Applicability: The overall applicability of the consortium’s preliminary research is to understand the interaction between pre-cancer cells and their local environment to determine what factors play a role in the ability of pre-cancer cells to invade and metastasize. This work will elucidate the evolution of pre-cancer cells and identify what factors can prevent or allow these cells to invade into surrounding tissues. The benefits of defining these processes will lead to the discovery of new biomarkers and treatment approaches. We will characterize precursor lesions and invasive tumors across genomic platforms due to our ability to work with very small tissue samples. We will learn which precursor lesions are likely to progress to or be associated with invasive cancer and which will remain localized. The risks of the proposal are strictly technical in that working with very small tissue samples that are found in precursor lesions is challenging. However, this is necessary in order to study the origins of ovarian cancers, and we have years of experience optimizing methods for this purpose. We also have already collected the tissue samples that will be required to perform these studies and, therefore, are well suited to quickly begin data generation. Within the first 2 years of funding, we will have determined the interactions between pre-cancer lesions and their local environment. This understanding can then lead to immediate testing of any new biomarkers in patient samples. These biomarkers can also be immediately incorporated into clinical trials of prevention and early detection for validation. Impact on the Ovarian Cancer Field: This consortium will create a multi-institutional collaboration with an outstanding track record of applying state-of-the-art technologies to study pre-cancer lesions and invasive diseases, as well as a wealth of experience in clinical practice, cancer biology, genomics, and computational medicine. The consortium will allow participating investigators to share their prior experience in ovarian cancer research and unify their complementary skills to focus on the common goal of ovarian cancer early detection. The team will create new knowledge for the unmet need to understand how normal tissues and pre-cancer cells obtain the capacity to invade and spread. We will deposit all data into the public domain so that other members of the ovarian cancer research community can use these data for secondary analyses and future unforeseen applications in biomarker and drug discovery. The consortium will also bring together scientists and consumer advocates to share knowledge that can subsequently be transferred to the larger scientific and advocacy communities. In addition, the consortium development will allow the planning of future studies of circulating and shed biomarkers, as well as the role of stem cells in precursor
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910232
Entities
People
- Douglas A Levine
Organizations
- Grossman School of Medicine
- United States Army