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

AUTHORS: Joshua D. CohenAmmar A. JavedChristopher ThoburnFay WongJeanne TiePeter GibbsMax SchmidtMichele T. Yip-SchneiderPeter J. AllenMark SchattnerRandall E. BrandAatur D. SinghiGloria M. PetersenSeung-Mo HongSong Cheol KimMassimo FalconiClaudio DoglioniMatthew J. WeissNita AhujaJin HeMartin A. MakaryAnirban MaitraSamir M. HanashMarco Dal MolinYuxuan WangLu LiJanine PtakLisa DobbynJoy SchaeferNatalie SillimanMaria PopoliMichael G. GogginsRalph H. HrubanChristopher L. WolfgangAlison P. KleinCristian TomasettiNickolas PapadopoulosKenneth W. Kinzler, Bert Vogelstein and Anne Marie Lennon

 JOURNAL: Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10202-10207. doi: 10.1073/pnas.1704961114. Epub 2017 Sep 5.


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. KRASmutations 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'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.

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