Molecular Characterization of Very Small Nuclear Circulating Tumor Cells: A Putative Biomarker for Visceral Metastasis in Prostate Cancer
Abstract
Metastatic, castration-resistant prostate cancer (mCRPC) may exhibit varied clinical courses. Some mCRPC patients will develop metastasis beyond the bone and lymph nodes, including the liver, lungs, and adrenal glands. These conditions are termed visceral metastases (VM). Patients with VM have significantly poorer overall survival than patients with non-VM, as their clinical course involves rapid deterioration from organ failure. Certain CRPC treatments have been shown to push the progression of the cancer to its more aggressive VM form. This highlights the importance of developing a means of detecting and predicting cancer progression to the viscera. Using the NanoVelcro Chip designed to capture circulating tumor cells (CTCs), we identified a morphologically unique subgroup of these cells, which we termed very small-nuclear CTCs (vsnCTCs). We found that these vsnCTCs appear in patients with VM and begin emerging before the disease progresses to VM. Thus, we hypothesize that vsnCTCs are associated with the development of VM and are biologically distinct from non-vsnCTCs, which lead to a different clinical course. We aim to analyze the association between vsnCTCs and VM, as these cells could play a key role in detection VM. Additionally, we aim to compare the gene expression of vsnCTCs and non-vsnCTCs to gain greater insight into the biology of VM. Dr. Jie-Fu Chen, the project s Principal Investigator, aspires to become a translational physician-scientist in field of prostate cancer metastasis. His goal is to develop new blood-borne biomarkers to detect and monitor aggressive subsets of prostate cancer. Dr. Chen plans to head a research team focused on translational studies with CTC-based assay in prostate cancer. Through his postdoctoral research training under the mentorship of Dr. Edwin Posadas at Cedars Sinai Medical Center (CSMC), Dr. Chen designed and executed clinical studies with prostate cancer. He wishes to further his training by enrolling in courses at the University of California in Los Angeles in molecular biotechnology, oncology, methodology of clinical trials, advanced biostatistics, and bioinformatics. He also aims to attend the Clinical Scholars Program, as well as the Clinical and Translational Research Workshop at CSMC to acquire new skills and guidance in his translational medicine work. He will continue training under his mentors, Dr. Edwin Posadas and Dr. Hsian-Rong Tseng, giving him a unique combination of clinical and bioengineering backgrounds to further his studies of CTCs in prostate cancer. Through our research, we aim to confirm the association between vsnCTCs and VM. Moreover, we intend to characterize these cells and identify the mechanism underlying VM disease progression. The overarching goal of our research inquiry is to develop of a new assay for predicting VM. This is an important an unmet need for prostate cancer clinical care as hormonal treatments drive more patients conditions towards VM. By identifying men early in their transition to this more aggressive, VM-disposed disease, oncologists can implement therapy that will alter the natural history of VM in prostate cancer. Our studies will elucidate the biological differences between VM and non-VM prostate cancer, as revealed through CTC and tissue analysis, and lead to refined therapeutic strategies. Our work will lead to significant progress toward a putative biomarker for aggressive prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610638
Entities
People
- Jie-fu Chen
Organizations
- Cedars-Sinai Medical Center
- United States Army