A Novel Blood-Based RNA Assay for Early Detection of Lethal Prostate Cancers
Abstract
Prostate cancer (PCa) is the most common cancer among men in the United States. It is also the third leading cause of cancer death for men in the country, accounting for more than 26,000 deaths annually. Men who develop metastatic disease are considered incurable and at risk for pain and death from PCa; thus, it is imperative to detect aggressive disease early and adjust treatment accordingly. However, there are little examination methods used currently in the clinic to measure aggressiveness beyond Gleason grading system, serum PSA, and clinical exam. New clinical genomic assays are useful for predicting outcomes based on genomic signatures that reflect disease aggressiveness; however, the limitation of these genomic assays is the need for tissue biopsy. Given the risk and invasiveness of the procedure, a non-invasive assay with the reference to molecular features driving clinical behavior and outcomes would potentially address this unmet need in PCa. Recently, our team developed an assay, called the Thermoresponsive (TR)-NanoVelcro assay, which allows for the capture and release of prostate circulating tumor cells (CTCs) in blood with intact RNA information. We combined this technology with NanoString’s nCounter platform, which can accurately quantify the expression of RNA, making it possible to perform a RNA-based prostate cancer classification panel named the PCS panel. This PCS panel categorizes PCas into subtypes that are related to patients’ disease courses, such as time to progression on therapy, metastatic pattern, sensitivity or resistance to various therapies, and death from PCa, as measures of aggressiveness. By studying the CTCs of prostate cancer, we are able to obtain the information of cancer through a blood test, without undergoing the risky and invasive procedure of biopsy. Through our research, we aim to develop a novel blood-based assay for the detection of aggressive prostate cancer using CTC-based RNA information, which could help physicians detect the patients’ aggressive disease in a timely manner and adjust treatment accordingly, thus making a significant difference in the disease’s natural course and survival time. Dr. Yu Jen Jan, the project’s Principal Investigator, aspires to become a translational physician-scientist in the field of prostate cancer. His goal is to develop new blood-borne biomarkers to detect and monitor aggressive subsets of prostate cancer. Dr. Jan plans to lead 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. Jan designed and executed clinical studies on the topic of prostate cancer. He wishes to further his training by attending 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. The overarching goal of our research is to develop strategies to prevent progression to lethal prostate cancer. Using this our assay, we can detect the forthcoming appearance of drug resistance and metastasis progression in patients with prostate cancers, which will lead to timely adjustment of therapeutic strategies that could potentially alter the disease’s natural course, preventing progression to lethal prostate cancer. Our research will develop a new, non-invasive, blood-based assay with wide detection spectrum from early to aggressive stages of the disease, which will be useful for detecting emerging drug resistance and metastatic progression. In the era of precision medicine, our work will lead to significant progress toward screening and surveillance for prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810576
Entities
People
- Yu Jen Jan
Organizations
- Cedars-Sinai Medical Center
- United States Army