Research Papers:
NOTUM is a potential pharmacodynamic biomarker of Wnt pathway inhibition
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Babita Madan1, Zhiyuan Ke2, Zheng Deng Lei1, Frois Ashley Oliver1, Masanobu Oshima3, May Ann Lee2, Steve Rozen1, David M. Virshup1,4
1Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore
2Experimental Therapeutics Centre, A*STAR, Biopolis, Singapore
3Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
4Department of Pediatrics, Duke University, Durham, NC, USA
Correspondence to:
David M. Virshup, e-mail: [email protected]
Babita Madan, e-mail: [email protected]
Keywords: Wnt signaling, Notum, Biomarker, PORCN inhibitor
Received: September 06, 2015 Accepted: January 23, 2016 Published: February 03, 2016
ABSTRACT
Activation of Wnt signaling due to Wnt overexpression or mutations of Wnt pathway components is associated with various cancers. Blocking Wnt secretion by inhibiting PORCN enzymatic activity has shown efficacy in a subset of cancers with elevated Wnt signaling. Predicting response to upstream Wnt inhibitors and monitoring response to therapeutics is challenging due to the paucity of well-defined biomarkers. In this study we identify Notum as a potential biomarker for Wnt driven cancers and show that coordinate regulation of NOTUM and AXIN2 expression may be a useful predictor of response to PORCN inhibitors. Most importantly, as NOTUM is a secreted protein and its levels in blood correlate with tumor growth, it has potential as a pharmacodynamic biomarker for PORCN and other Wnt pathway inhibitors.