Determine the Dynamic Response to Androgen-Blockade Therapy in Circulating Tumor Cells of CRPC Patients by Transcription-Based Reporter Vectors
Abstract
What is the rationale of pursuing CTCs in prostate cancer? Prostate cancer is the most common form of cancer among American men, afflicting about 1 out of 6 men in their lifetime. Although the disease is not aggressive in the majority of patients, about 20% of the cases can evolve to the fatal form, namely metastasis. At this stage, cancer cells have escaped from the prostate gland, and invaded other vital organs, bringing the 5-year survival rate down to lower than 40%. Circulating tumor cells (CTCs) are cells that are shed by prostate cancer and other solid tumors; they transit through the bloodstream and are believed to seed metastasis at distant vital organs. Thus, the number of CTCs increases greatly in advanced, metastatic stage of prostate cancer. However, among the great number of red and white blood cells in a patient s bloodstream, CTCs are very rare and difficult to isolate. Given the deadly consequence of CTCs, achieving optimal detection and capturing of CTCs is currently a paramount priority in oncology. What are the scientific objectives of this proposed project? Scientists and clinicians believe CTCs can be exploited as a "non-invasive liquid biopsy" to gain real-time information on the cancer. Toward this goal, this technology-driven project aims to improve upon the CTC detection method to allow interrogation of "functional activities" in CTCs such as therapeutic responses to drugs. Currently, there is a Food and Drug Administration (FDA)-approved CTC detection technology (CellSearch), which relies on an epithelial cell surface protein (EpCAM) to identify CTCs. Some of the limitations of the current technology include inefficient capture of CTCs and its inability to determine viability of captured cells or specifically identify CTCs of prostate cancer origin. The dedicated efforts of our team member Professor Tseng and his research group have contributed greatly to advance the CTC capturing technology. They have engineered small devices, so-called microfluidic chips, with greatly increased adhering surface areas to capture CTCs. Their patented "nano-Velcro" technology has been shown to achieve up to 100-fold higher efficiency in capturing CTCs than the current approved method. This project aims to boost the performance of the nano-Velcro microfluidic CTC capturing technology in three important aspects, namely, to not only identify cells that are viable and of prostate origin but also to determine the CTCs therapeutic response to androgen blockade therapy. The initiating PI Professor Wu s long-standing research has been in developing a "reporter" technology that uses an engineered, common-cold virus to turn on a light signal only in living, prostate cancer cells. By using a prostate-specific virus that produces red fluorescent protein, the research group showed that they were able to "light" up prostate cancer CTCs fluorescently amongst patients blood cells. The molecular switch that controls the fluorescent protein production in the reporter virus is regulated by androgen. Thus, this technology can be used to assess treatment response to newly FDA-approved androgen blocking drugs such as abiraterone and enzalutamide in CTCs directly by the change in light signal intensity in the CTCs. What is the clinical applicability of this new CTC detection technology? This technology will be most useful in aiding the personalized diagnostic and treatment decision for patients with castration resistant prostate cancer (CRPC) or metastatic disease. By estimate, over 20,000 men per year will likely advance to this stage, at which time the newly approved abiraterone and enzalutamide will be an excellent treatment option for this group of patients. However, the treatment response to these drugs is far from uniform. Thus, the new technology proposed here could be used to determine the likelihood of responding to these drugs in the patient s CTCs before the start of treatment. Under the guidan
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510256
Entities
People
- Lily Wu
Organizations
- United States Army
- University of California, Los Angeles