The Canary Center for Cancer Early Detection at Stanford fosters research programs based on the hypothesis that effective early cancer detection and management will require a combination of blood and molecular imaging tests. The center is bringing together physicians and scientists that work in the areas of in vitro and in vivo diagnostics to advance cancer patient care with an initial focus on lung, ovarian, pancreatic and prostate cancers. PSA testing currently serves as the cornerstone for prostate cancer screening and management. However, because PSA suffers from imperfect sensitivity and specificity, prostate cancer is frequently under- and over- diagnosed, resulting in missed cancers and unnecessary biopsies. Better methods are needed to accurately detect prostate cancer, and to determine its capacity for progression. This proposal leverages strengths at the Schools of Medicine and Engineering at Stanford University, the Stanford Cancer Center, the Canary Foundation, and the National Cancer Institute, including a center for cancer nanotechnology excellence (CCNE) U54 and an in vivo cellular and molecular imaging center (ICMIC) P50. We also form important links to faculty at the Fred Hutchinson Cancer Center. In this proposal we outline two distinct and complementary strategies for applying cutting edge technologies to the dual approach for the detection and management of prostate cancer. In Project #1 we propose the adaptation of our newly-developed magneto-nanosensor to the multiplex analysis of blood-based biomarkers for prostate cancer detection and prognostication. This platform is 1000-fold more sensitive than an ELISA assay, has 64-multiplex capacity, and spans a dynamic range of 6 decades, enabling the interrogation of complex biomarker panels designed for high sensitivity and specificity. In project #2 we propose the adaptation of our latest ultrasound technology using tumor angiogenesis-targeted microbubbles to image prostate cancer. Microbubbles are gaseous bubbles encased by lipid shells functionalized with antibodies that target tumor-associated angiogenesis. When introduced into the bloodstream before imaging, VEGFR2-targeted microbubbles bind to the endothelial cells of the tumor neovasculature to provide enhanced contrast during ultrasound. Incorporated into TRUS (transrectal ultrasound), this approach will increase the accuracy of detection during the screening process. Our long-term goal is to combine our blood-based biomarker and imaging approaches to the accurate early detection and prognostication of prostate cancer.
Our proposed work will improve cun'ent prostate cancer screening methods by increasing the accuracy of detection and prognosis, and reducing the numbers of unnecessary surgeries. Prostate cancer patients will initially benefit and then the strategies employed will be able to help other cancer patients as well.
|Zackrisson, S; van de Ven, S M W Y; Gambhir, S S (2014) Light in and sound out: emerging translational strategies for photoacoustic imaging. Cancer Res 74:979-1004|
|Yu, Yan P; Ding, Ying; Chen, Zhanghui et al. (2014) Novel fusion transcripts associate with progressive prostate cancer. Am J Pathol 184:2840-9|
|Chen, Zuxiong; Gulzar, Zulfiqar G; St Hill, Catherine A et al. (2014) Increased expression of GCNT1 is associated with altered O-glycosylation of PSA, PAP, and MUC1 in human prostate cancers. Prostate 74:1059-67|
|Brooks, James D (2013) Managing localized prostate cancer in the era of prostate-specific antigen screening. Cancer 119:3906-9|
|Brooks, James D (2012) Translational genomics: the challenge of developing cancer biomarkers. Genome Res 22:183-7|
|Hori, Sharon S; Gambhir, Sanjiv S (2011) Mathematical model identifies blood biomarker-based early cancer detection strategies and limitations. Sci Transl Med 3:109ra116|
|Jokerst, Jesse V; Lobovkina, Tatsiana; Zare, Richard N et al. (2011) Nanoparticle PEGylation for imaging and therapy. Nanomedicine (Lond) 6:715-28|