Determinants of Distant Metastatic Spread in High-Grade Serous Ovarian Cancer
Abstract
More than one in three American women develop cancer at some point in their lives, including women in the U.S. military and the nearly 2 million female Veterans. In 2021 alone, an estimated 21,000 women in the U.S. will be diagnosed with ovarian cancer. Unfortunately, almost 65% of women diagnosed with ovarian cancer will die within 5 years of their diagnosis. Metastasis is the process of cancer cells spreading to different parts of the body, often through the blood stream. High-grade serous ovarian cancer (HGSC), the most common type of ovarian cancer, primarily spreads to organs within the abdomen without entering the circulation – known as local spread. Even when a patient with HGSC has extensive abdominal disease, metastasis to organs via the blood stream, such as the liver, lungs, or brain (distant spread), is uncommon. This is a unique feature of HGSC and is in contrast to other cancers such as breast or colorectal cancer, where metastatic spread to distant organs such as the liver, lung, brain, or bone is frequently seen. We currently have a very limited understanding why some patients with HGSC will develop distant metastatic disease and those that do have a poorer prognosis compared to women with abdominally confined disease. Given this disparity in patient outcomes and the unusual pattern of organ involvement, the metastatic process in HGSC deserves attention. In order to understand why distant metastasis occurs in some patients, but not others, tumor tissue from local and distant sites from the same patient is needed to identify which features are unique to distant metastatic tumors that have enabled them to grow in those organs. Additionally, normal tissue from distant sites with and without metastases are needed to understand if factors in normal cells contribute to the ability of metastatic cancer cells to grow. However, collection of such tissue from HGSC patients is a major challenge as surgery once distant metastases have formed rarely occurs. We have successfully collected matched local and distant tumor samples, as well as normal tissue, through our research autopsy program. In this study, we will make use of our unique collection of samples to examine the biological characteristics of metastatic HGSC samples and normal tissues, which we anticipate will ultimately lead to identification of new approaches to treat or prevent metastasis in HGSC. Specifically, we will (1) profile paired local and distant metastatic tumor samples to identify features that are unique to distant metastases, (2) examine apparently tumor free (normal) tissue to determine whether tumor cells have actually metastasized to those organs but have not grown into metastases, (3) compare the characteristics of normal tissue surrounding metastases, individual tumor cells, and entirely tumor-free samples to identify factors that limit the growth of metastatic cancers. By performing comprehensive analysis of local and distant metastatic tumors, as well as normal tissue, we will begin to better understand which factors influence metastatic spread. This pilot study will provide significant preliminary data for future research that will involve developing and validating models of metastasis that can subsequently be utilized to identify new therapeutic targets for the treatment and prevention of metastatic disease. We firmly believe that fully understanding the metastatic process in HGSC will lead to improved patient care and better outcomes for all women diagnosed with HGSC. This study is directly aligned with the research recommendations made by the congressionally mandated Metastatic Task Force, and we anticipate that it will lessen the impact of ovarian cancer on U.S. military force readiness by reducing the need for medical retirement due to metastatic cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210359
Entities
People
- Elizabeth L Christie
Organizations
- United States Army
- University of Melbourne