Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers

Joshua D. Cohen(Howard Hughes Medical Institute), Ammar A. Javed(Johns Hopkins University), Christopher J. Thoburn(Johns Hopkins University), Fay Wong(Howard Hughes Medical Institute), Jeanne Tie(The University of Melbourne), Peter Gibbs(The University of Melbourne), C. Max Schmidt(Indiana University School of Medicine), Michele Yip-Schneider(Indiana University School of Medicine), Peter J. Allen(Memorial Sloan Kettering Cancer Center), Mark Schattner(Memorial Sloan Kettering Cancer Center), Randall E. Brand(University of Pittsburgh), Aatur D. Singhi(University of Pittsburgh), Gloria M. Petersen(Mayo Clinic in Florida), Seung‐Mo Hong(Ulsan College), Song Cheol Kim(Ulsan College), Massimo Falconi(San Raffaele University of Rome), Claudio Doglioni(San Raffaele University of Rome), Matthew J. Weiss(Johns Hopkins University), Nita Ahuja(Johns Hopkins University), Jin He(Johns Hopkins University), Martin A. Makary(Johns Hopkins University), Anirban Maitra(The University of Texas MD Anderson Cancer Center), Samir Hanash(The University of Texas MD Anderson Cancer Center), Marco Dal Molin(Johns Hopkins University), Yuxuan Wang(Howard Hughes Medical Institute), Lu Li(Johns Hopkins University), Janine Ptak(Howard Hughes Medical Institute), Lisa Dobbyn(Howard Hughes Medical Institute), Joy Schaefer(Howard Hughes Medical Institute), Natalie Silliman(Howard Hughes Medical Institute), Maria Popoli(Howard Hughes Medical Institute), Michael Goggins(Johns Hopkins University), Ralph H. Hruban(Johns Hopkins University), Christopher L. Wolfgang(Johns Hopkins University), Alison P. Klein(Johns Hopkins University), Cristian Tomasetti(Johns Hopkins University), Nickolas Papadopoulos(Johns Hopkins University), Kenneth W. Kinzler(Johns Hopkins University), Bert Vogelstein(Howard Hughes Medical Institute), Anne Marie Lennon(Johns Hopkins University)
Proceedings of the National Academy of Sciences
September 5, 2017
Cited by 569Open Access
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Abstract

Significance Few patients with pancreatic cancer survive longer than 5 y, in part because most patients are identified only after their disease has progressed to an advanced stage. In this study, we show how combining mutations in circulating tumor DNA (ctDNA) with protein markers can result in a screening test with improved sensitivity while retaining specificity. The combination of the ctDNA and protein markers was superior to any single marker. Moreover, the combination detected nearly two-thirds of pancreatic cancers that had no evidence of distant metastasis at the time of surgical resection. The strategy may represent an approach to detect cancers of many types at an earlier stage.


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