ABSTRACTNearly 240,000 men are diagnosed with prostate cancer (PCa) every year in the United States but there is noclinical test that can effectively determine whether their tumors will progress to life-threatening disease or remainindolent. Consequently, a majority of men with low-risk PCa who should simply undergo active surveillance (AS)instead receive costly treatments with major long-term adverse effects. A multidisciplinary team of investigatorscomprising clinicians, biologists, and bioengineers, who individually have developed key technologies, now seekto combine resources to directly address this long-standing clinical problem. The proposed project focuses onvalidating a novel technology platform that combines label-free and quantum dot-labeled spectral imaging topredict PCa progression. Illustrating the need and utility of our technology is the specific choice of assays weare utilizing here. The Mayo team has shown that rearrangements and/or copy number variant levels of fivegenomic regions in tumor cells in formalin fixed and paraffin embedded (FFPE) biopsy specimens can be usefulin determining risk of PCa aggressiveness. However, these markers cannot be developed into a robust, clinicalassay due to the current limitations of technology: Needle biopsy specimens often contain only a small amountof cancer, and even when cut into thin sections, the employment of a 5-probe assay is often simply not possiblebecause of the limited capacity to multiplex conventional FISH probes. Furthermore, it is not possible tosimultaneously identify cell types in sections labeled for fluorescence, so it is not clear whether cells that stainpositive or negative for the FISH probes comprise cancer or stromal cells. This is the general problem ourtechnology will address ? lack of multiplexed molecular quantitation and identification of (non)responsive cells.The Illinois team has shown that using infrared (IR) spectral imaging, the tumor microenvironment can be profiledand new predictive information can be obtained. However, this approach needs to be validated in a larger trial.Our project addresses the technology and validation needs by combining (a) FISH-probes based on quantumdots to identify specific molecular alterations with (b) cell/tissue identification using label-free infraredspectroscopic imaging. While both technologies has been independently developed and demonstrated to beeffective, they have not been integrated in a complementary manner nor together used to address PCa needs.Here, we propose a test and validation of this combination technology via a cohort of PCa specimens that havealready been genomically profiled. The combined technology's validation will also test its effectiveness inproviding a practical test for PCa prognosis with statistical models and measures that will be compared to thecurrent gold standards. Success in this proposal will enable the production of a robust assay strategy todetermine which men are best candidates for AS or for more aggressive treatment ? which would betransformative for prostate healthcare. Validation of this technology also paves the way for combined molecularand cellular analysis in all tissues and for all types of molecular targets, which can vastly expand our capacity toprovide accurate and specific diagnoses that can guide therapy in a wide range of pathologies.
|Effective start/end date||8/4/16 → 7/31/19|
- National Institutes of Health: $387,693.00