Ovarian cancer patient prognosis and quality of life are significantly affected by the failure to accurately diagnose disease at early stage, a lack of timely information regarding response to treatment, and a slow response to relapse. The five-year survival rate for all ovarian cancer cases is just 44%. Diagnosis after dissemination hinders prognosis, although the five-year survival rates is 91% when diagnosed at stage I. Detection of ovarian cancer in high-risk populations, improved monitoring of patient response to treatment, and detection of disease relapse would markedly improve survival rates.Current detection methods consistently fail to alter patient outcome or reduce mortality. It would also be beneficial to develop individualized treatment plans by giving physicians the ability to monitor patient response more quickly and frequently. This would improve and accelerate the testing of therapeutic regimens, including personalized treatments, towards improving patient survival and quality of life.
The long-term goal of our work is to develop a real-time biosensor that will enable non-invasive, patient-centered monitoring of intrauterine biomarkers for early ovarian cancer detection in at-risk patients, treatment response, and disease recurrence. The objective of this project is to develop a robust implantable nanosensor platform offering sensitivity, selectivity, and rapid response, to address these needs. Dr. Douglas Levine’s laboratory has found that uterine washings in patients with high-grade serous carcinoma (HGSC) contain elevated levels of several biomarkers including HE4 and YKL-40 . The ability to measure these proteins on-demand within the uterus would allow excellent sensitivity and selectivity of ovarian cancer detection.
In this project, I plan to develop an implantable biosensor which will allow rapid, real-time and highly-sensitive detection of each of five biomarkers within the uterine cavity in the form of an intrauterine (IUD) device modified to contain the single-walled carbon nanotubes sensor (SWNT) for implantation in the human uterus. The proposed biosensor will harness the unique optical properties and sensitivity of SWNT. Nanotubes emit near-infrared fluorescence that is not bleached or absorbed by the body tissue – this property is ideal for long-term in vivo sensing. The final sensor will contain two different SWNT populations, each detecting one of the HGSC-specific biomarkers. This technology will provide accurate measurements of each biomarker and will alert if their local levels will start to elevate in patients at high risk for HGSC or patients that will have relapse following a treatment. The technology will be novel in detection mechanisms in both sensitivity and specificity by using the diagnostic potential and site-specific quantification of the two biomarkers. This technique will significantly reduce the time and effort needed to diagnose ovarian cancer and lead to a robust, point-of-care early-stage diagnosis.
This research has been generously supported by Ovarian Cycle, Tampa, FL.
Dr. Zvi Yaari is currently a postdoctoral research fellow at the Memorial Sloan Kettering Cancer Center, (MSKCC) New York City, NY in the laboratory of Dr. Daniel A. Heller. Dr. Yaari received his B.Sc., M.Sc and Ph.D in Chemical Engineering from the Technion – Israel Institute of Technology. During his Ph.D studies, Dr. Yaari rationally designed a high-throughput screening technology for matching cancer patients with the most potent anticancer agent in a personalized manner. The technology is based on barcoded liposomes that contain various anticancer agents and a unique dsDNA as a barcode that correlates with the drug activity. This technology allows screening various of drugs simultaneously inside the patient body and has a single cell resolution. Dr. Yaari realized that the goal of his life is to harness his engineering skills to create new technologies for improving cancer care in general and help cancer patients in particular. For him, Memorial Sloan Kettering Cancer Center (MSKCC) was the ultimate institution to achieve this goal.
Dr. Yaari’s current research focus is on developing an implantable nanosensor for early-stage detection of ovarian cancer. He is designing a nano sensor that is based on Single Walled Carbon Nanotubes (SWCNTs). The SWCNTs allow detection in very high sensitivity and precision due to their unique photoluminescence properties in the near infrared (NIR) range. Currently he is studying how the interactions of the SWCNTs with various of ovarian cancer biomarkers can cause a shift in the emitted wavelengths or affect the emitted intensity. The goal is to implant the sensor inside an intrauterine device (IUD) and to monitor the initiation and progression of ovarian cancer. Dr. Yaari is mentoring graduate students and collaborating with clinicians and product engineers.
Dr. Yaari received several awards for his graduate work, including the Dan David Prize, Rappaport Prize, Jacobs Excellence Award, Prize for Excellence in Science from the Department of Chemical Engineering and the 1st Prize for outstanding graduate research from The Israeli Chapter of the Controlled Release Society (ICRS).