@article{f2289b999033410f8b37ec3d6efe1f10,
title = "Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers",
abstract = "The earlier diagnosis of cancer is one of the keys to reducing cancer deaths in the future. Here we describe our efforts to develop a noninvasive blood test for the detection of pancreatic ductal adenocarcinoma. We combined blood tests for KRAS gene mutations with carefully thresholded protein biomarkers to determine whether the combination of these markers was superior to any single marker. The cohort tested included 221 patients with resectable pancreatic ductal adenocarcinomas and 182 control patients without known cancer. KRAS mutations were detected in the plasma of 66 patients (30%), and every mutation found in the plasma was identical to that subsequently found in the patient{\textquoteright}s primary tumor (100% concordance). The use of KRAS in conjunction with four thresholded protein biomarkers increased the sensitivity to 64%. Only one of the 182 plasma samples from the control cohort was positive for any of the DNA or protein biomarkers (99.5% specificity). This combinatorial approach may prove useful for the earlier detection of many cancer types.",
keywords = "Circulating tumor DNA, Early cancer detection, Liquid biopsy, Pancreatic cancer, Protein biomarkers",
author = "Cohen, {Joshua D.} and Javed, {Ammar A.} and Christopher Thoburn and Fay Wong and Jeanne Tie and Peter Gibbs and Schmidt, {C. Max} and Yip-Schneider, {Michele T.} and Allen, {Peter J.} and Mark Schattner and Brand, {Randall E.} and Singhi, {Aatur D.} and Petersen, {Gloria M.} and Hong, {Seung Mo} and Kim, {Song Cheol} and Massimo Falconi and Claudio Doglioni and Weiss, {Matthew J.} and Nita Ahuja and Jin He and Makary, {Martin A.} and Anirban Maitra and Hanash, {Samir M.} and {Dal Molin}, Marco and Yuxuan Wang and Lu Li and Janine Ptak and Lisa Dobbyn and Joy Schaefer and Natalie Silliman and Maria Popoli and Goggins, {Michael G.} and Hruban, {Ralph H.} and Wolfgang, {Christopher L.} and Klein, {Alison P.} and Cristian Tomasetti and Nickolas Papadopoulos and Kinzler, {Kenneth W.} and Bert Vogelstein and Lennon, {Anne Marie}",
note = "Funding Information: J. Brooks, K. Chaffee, and W. Bamlet of the Mayo Clinic; and Dr. Herb Zeh of the University of Pittsburgh for their assistance with enrollment for this study. This work was supported by the Lustgarten Foundation for Pancreatic Cancer Research, The Virginia and D.K. Ludwig Fund for Cancer Research, The Conrad N. Hilton Foundation, The Sol Goldman Center for Pancreatic Cancer Research, The Michael Rolfe Pancreatic Cancer Research Foundation, The Joseph L. Rabinowitz Fund for Pancreatic Cancer Research, Susan Wojcicki and Dennis Troper, The Benjamin Baker Scholarship, The Commonwealth Foundation, National Health and Medical Research Council Grant APP1060804, The John Templeton Foundation, and NIH Grants P30-CA006973, P50-CA062924, P50-CA102701, CA06973, CA152753, CA196403, CA200468, GM-07309, and U01CA152753. Publisher Copyright: {\textcopyright} 2017, National Academy of Sciences. All rights reserved.",
year = "2017",
month = sep,
day = "19",
doi = "10.1073/pnas.1704961114",
language = "English (US)",
volume = "114",
pages = "10202--10207",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "38",
}