The long-term goal of this R01 proposal is to develop a circulating tumor cell-based assay to identify prostate cancer (PCa) patients who are at risk for developing visceral metastasis (VM). Drs. Posadas (Cedars-Sinai) and Tseng (CytoLumina) have formed a unique and functional academic/industrial partnership geared toward this project. VM in metastatic, castration-resistant PCa (mCRPC) is an emerging and unaddressed problem. Patients with VM have significantly foreshortened cancer-specific survival and die from organ failure in a fashion distinct from patients with bone-predominant disease. VM are typically found on imaging requested only when organ function is already compromised-typically late in the clinical course but affect over 45% of patients with advanced PCa. Early treatment can improve outcome but this requires timely detection. Thus, there is an unmet need to identify patients at risk for VM to customize imaging surveillance and create an opportunity to alter disease trajectory. Circulating tumor cells (CTCs) are rare cancer cells that can be isolated from whole blood. The NanoVelcro assay is a novel cellular isolation technology introduced by CytoLumina that is capable of identifying CTCs in small volumes of blood (as little as 1 mL). Use of NanoVelcro assay has led to the identification of CTC subsets based on nuclear morphology including those with nuclei less than 8.5 m in diameter called very small nuclear CTCs (vsnCTCs). We have found that the appearance of vsnCTCs is associated with the presence of VM in men with PCa. We hypothesize that vsnCTCs appear before the VM are detectable by conventional radiographic assessment in mCRPC. This hypothesis will be tested by (aim 1) an analysis of CTC samples that have been serially collected over the past 3 years in our annotated CTC/blood bank ? a unique and invaluable resource for this work and, (aim 2) a prospective CTC analysis of men with mCRPC. Our early work shows that vsnCTCs appear months before the VM are detectable by conventional imaging techniques. This investigative project will create an opportunity for early imaging and therapy which can change the clinical course for patients. As a byproduct, this work will create a new clinical space in PCa by identifying men at risk for VM. The NanoVelcro vsnCTC Assay will provide a simple, minimally-invasive, and cost-effective means of identifying mCRPC patients at risk for VM, thereby allowing physicians to personalize patient monitoring, treatment, and therapy.

Public Health Relevance

Visceral metastasis (VM) in prostate cancer (PCa) is spread of cancer to organs such as the lungs and liver (rather than bone or lymph nodes). VM are clinically important and point toward a reduction in survival, but they are often found late when organ function is compromised. The long-term goal of this academic-industrial partnership R01 proposal is to introduce a new, low- cost, diagnostic technology that will identify patients at risk for VM to facilitate early detection of VM in PCa.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Mckee, Tawnya C
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Cedars-Sinai Medical Center
Los Angeles
United States
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Jan, Yu Jen; Chen, Jie-Fu; Zhu, Yazhen et al. (2018) NanoVelcro rare-cell assays for detection and characterization of circulating tumor cells. Adv Drug Deliv Rev 125:78-93
Cavassani, Karen A; Meza, Rebecca J; Habiel, David M et al. (2018) Circulating monocytes from prostate cancer patients promote invasion and motility of epithelial cells. Cancer Med 7:4639-4649
Shen, Mo-Yuan; Chen, Jie-Fu; Luo, Chun-Hao et al. (2018) Glycan Stimulation Enables Purification of Prostate Cancer Circulating Tumor Cells on PEDOT NanoVelcro Chips for RNA Biomarker Detection. Adv Healthc Mater 7: