Colorectal cancer (CRC) remains the second leading cause of cancer deaths among Americans largely due to inability to screen the ~100 million Americans >/=50 years old with colonoscopy because of the expense, discomfort, potential complications and lack of adequate endoscopic capacity. This is juxtaposed with the inefficiency of screening colonoscopies in that only ~5-6% yield """"""""screening relevant neoplasia"""""""" (advanced adenomas or early CRC). Even in patients with a personal history of adenomas and thus deemed to be at higher risk, the yield of surveillance colonoscopy is still <10%. Thus, there is an urgent need for a minimally intrusive risk stratification technique. Our biomarker development laboratory has focused on developing innovative light-scattering technologies to identify the micro-architectural correlates of the genetic/epigenetic changes in field carcinogenesis. We have used early techniques to prove that interrogation of the microscopically-normal rectal mucosa can predict concurrent neoplasia throughout the colon. In this competitive renewal, we plan to develop a novel technique, partial wave spectroscopy (PWS) that enables unprecedented quantitative characterization of the nanoscale architecture through analysis of brushed or extruded cells. Our preliminary data suggests that PWS signatures paralleled neoplastic progression in experimental models. In humans, rectal brushings were able to accurately predict concurrent neoplasia. These nanoscale alterations appear robust in that they represent a final common manifestation for heterogeneous genetic/epigenetic alterations. We propose to develop novel PWS signatures for prediction rule optimization and then use a training/testing set design to assess the ability to rectal PWS analysis to predict concurrent neoplasia in 1000 patients. We will assess another 500 patients to predict recurrence of personal history of adenomas (surveillance). Finally, we will explore novel approaches such as PWS analysis of fecal-derived colonocytes and compare the rectal PWS with molecular marker Muc 4 (developed in our BDL) and cellular markers (proliferation versus apoptosis). This should provide a highly accurate, minimally intrusive technique to allow risk-stratification and hence tailoring of CRC screening regimen.
Colorectal cancer is eminently potential through identification and removal of adenomatous polyps by colonoscopy. However, despite performing ~18-20 million colonoscopies per year, CRC kills 50,000 Americans per year. Because >90% of colonoscopies are negative for significant lesions, our goal is to develop a minimally-intrusive approach allow colonoscopy to cover more of the population but only patients likely to derive benefit from the test.
|Chowdhury, Sanjib; Roy, Hemant K (2017) The genetics and molecular biology of colonic neoplasia: practical implications for the clinician. Curr Opin Gastroenterol 33:47-52|
|Calderwood, Audrey H; Lasser, Karen E; Roy, Hemant K (2016) Colon adenoma features and their impact on risk of future advanced adenomas and colorectal cancer. World J Gastrointest Oncol 8:826-834|
|Roy, Hemant K; Brendler, Charles B; Subramanian, Hariharan et al. (2015) Nanocytological field carcinogenesis detection to mitigate overdiagnosis of prostate cancer: a proof of concept study. PLoS One 10:e0115999|
|Radosevich, Andrew J; Mutyal, Nikhil N; Eshein, Adam et al. (2015) Rectal Optical Markers for In Vivo Risk Stratification of Premalignant Colorectal Lesions. Clin Cancer Res 21:4347-4355|
|Mutyal, Nikhil N; Radosevich, Andrew J; Bajaj, Shailesh et al. (2015) In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa. Pancreas 44:735-41|
|Momi, Navneet; Backman, Vadim; Brendler, Charles B et al. (2015) Harnessing novel modalities: field carcinogenesis detection for personalizing prostate cancer management. Future Oncol 11:2737-41|
|Stypula-Cyrus, Yolanda; Mutyal, Nikhil N; Dela Cruz, Mart et al. (2014) End-binding protein 1 (EB1) up-regulation is an early event in colorectal carcinogenesis. FEBS Lett 588:829-35|
|Patel, Mihir; Gomes, Andrew; Ruderman, Sarah et al. (2014) Polarization gating spectroscopy of normal-appearing duodenal mucosa to detect pancreatic cancer. Gastrointest Endosc 80:786-93.e1-2|
|Cruz, Mart Dela; Wali, Ramesh K; Bianchi, Laura K et al. (2014) Colonic mucosal fatty acid synthase as an early biomarker for colorectal neoplasia: modulation by obesity and gender. Cancer Epidemiol Biomarkers Prev 23:2413-21|
|Wali, Ramesh K; Hensing, Thomas A; Ray, Daniel W et al. (2014) Buccal microRNA dysregulation in lung field carcinogenesis: gender-specific implications. Int J Oncol 45:1209-15|
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