Investigation of Circulating Tumor Cell Clusters as Potential Biomarkers for Aggressive Prostate Cancer in African American Patients
Abstract
One in seven men are expected to be diagnosed with prostate cancer in their lifetime, making the prostate cancer the second most common cancer in adult men. Incidence and mortality rates of prostate cancer are significantly different between different ethnic groups. African-Americans are disproportionately affected by prostate cancer by having not only the highest incidence and mortality rates, but also earlier mean age at diagnosis and survival period. The statistics show that compared to whites, African-Americans are more than two times more likely to be diagnosed with prostate cancer and also are more likely to die from it. Prostate cancer also spreads more aggressively in African American men. While this disparity can be attributed to many socioeconomic factors, the underlying biological factors behind this disparity are still unknown. Prostate cancer metastasis is mainly driven by tumor cells shed from the primary tumor into blood circulation. The isolation of these tumor cells, called circulating tumor cells (CTCs), from patient blood samples and analysis of their composition have the potential to provide valuable insights into the clinical disparity in the aggressiveness of prostate cancer metastasis in African American men. However, most of CTCs cannot remain viable in the bloodstream and fail to initiate metastasis. Therefore, an investigation on the aggressive spread of prostate cancer in African American patient population requires specifically targeting those CTCs with high metastatic propensity. Since the 1950s, clusters of CTCs, also called circulating tumor microemboli, are known to be more metastatic than single tumor cells. In fact, recent data show that they are 50 times more likely to grow tumor than single CTCs. Therefore, we hypothesize that that aggressive spread of prostate cancer in African American patients may be attributed to higher concentration and/or to unique morphological/molecular features of CTC-clusters in their bloodstream. Our application is uniquely positioned to test this hypothesis. First, we have developed a first-of-its-kind microchip technology that can specifically isolate live CTC-clusters from patient blood samples. Second, we have a large volume of African American men with prostate cancer in the State of Georgia that gives us a unique privilege to lead research efforts in this area. Finally, we propose a collaborative team effort that integrates bioengineering, bioinformatics, and clinical investigation for a comprehensive investigation. Our project will provide preliminary data on the potential clinical utility of CTC-clusters in guiding the therapy of African American patients with metastatic prostate cancer. If successful, our findings can potentially address multiple FY2019 overarching challenges by (1) transforming our understanding of prostate cancer prognosis in the disparity population by providing insights into the metastatic process at the cellular/molecular level; (2) helping identify new biomarkers as diagnostic and therapeutic targets, which can ultimately reduce the mortality rate in the disparity population; (3) impacting clinical management of cancer by monitoring the disease response following therapeutic interventions with serial minimally-invasive blood-based biopsies.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010649
Entities
People
- Ali Fatih Sarioglu
Organizations
- Georgia Tech Research Corporation
- United States Army