Development of a Novel Circulating Tumor Cell Population for Early Detection of Recurrent Colorectal Cancer
Abstract
Death from colorectal cancer has been declining over the past decade due in part to heightened awareness of preventative screening. Despite this, colorectal cancer remains the second leading cause of cancer-related death in the United States. This apparent lack of headway is attributed to the high death rate in patients with late-stage colorectal cancer (94%) and the astounding rate of return of disease in newly diagnosed colorectal cancer patients (32%) after they have been “successfully” treated. Not surprisingly, recurrent disease carries with it an increased risk of death, with an overall survival of only 14.3%. This highlights the lack of available biomarkers or sensors that can monitor the tumor across the continuum of disease and the spectrum of treatment response to provide important clues to tell the clinician if treatment is working, or in the case where treatment is completed, if the cancer is returning. Such a breakthrough would transform colorectal cancer survival. A primary barrier to timely identification of cancer progression is the lack of a screening test to identify cancer and the return of cancer after treatment. Our group has discovered a novel population of circulating tumor cells (CTCs) that are products of a blood cell and cancer cell fusing together (called circulating hybrid cells, CHCs). These fused cells demonstrate a quick way that a cancer cell can gain new properties from a second cell, giving it advantages and new identities. We have demonstrated that fusion hybrids have more aggressive, metastatic behaviors than unfused cancer cells. Further, the novel CHC population is detectible in human cancer patients at greater numbers than previously investigated CTCs. From our early studies and efforts, we believe that a test for CHCs using patient blood can be developed to identify a fingerprint of cancer to help us identify cancer earlier, or to identify if a cancer is responding to treatment or if it has returned. In addition, CHCs can be monitored after treatment and over time for early detection of recurrent disease to provide an opportunity for the earliest therapeutic intervention. The innovation in our proposed research is that CHCs are a new population of tumor cells that have never been studied in colorectal cancer patients, yet they have potential utility to be developed as a non-invasive addition to current tests. Our earlier studies in mice demonstrate that this new population of cells can form tumors with more intensity than conventionally defined CTCs, highlighting that the CHCs may have an important role in tumor regrowth. We anticipate that successful completion of the proposed studies will provide the foundation for development of a clinical trial to establish the effectiveness and utility of a CHC-based test for colorectal cancer. Colorectal cancer does not discriminate. The lifetime risk for acquiring colorectal cancer is 7%. Therefore, the risk for colorectal cancer for the over 3,000,000 Service men and women and their families will have an immense impact. Exploring new ways to detect and manage colorectal cancer will have a major impact on our military personnel and their families.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810621
Entities
People
- Melissa Wong
Organizations
- Oregon Health & Science University
- United States Army