title: NOTUM is a potential pharmacodynamic biomarker of Wnt pathway inhibition.
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.
authors: Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore.
authors: Babita
authors: B
authors: Madan
authors: Experimental Therapeutics Centre, A*STAR, Biopolis, Singapore.
authors: Zhiyuan
authors: Z
authors: Ke
authors: Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore.
authors: Zheng Deng
authors: ZD
authors: Lei
authors: Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore.
authors: Frois Ashley
authors: FA
authors: Oliver
authors: Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
authors: Masanobu
authors: M
authors: Oshima
authors: Experimental Therapeutics Centre, A*STAR, Biopolis, Singapore.
authors: May Ann
authors: MA
authors: Lee
authors: Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore.
authors: Steve
authors: S
authors: Rozen
authors: Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore.|Department of Pediatrics, Duke University, Durham, NC, USA.
authors: David M
authors: DM
authors: Virshup
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors; D000818:Animals; D060466:Axin Protein / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004950:Esterases / Q000096:biosynthesis*; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D064593:Heterografts; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014162:Transfection; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: C491761:AXIN2 protein, human; D060466:Axin Protein; D014408:Biomarkers, Tumor; C000620782:ETC-159; D006576:Heterocyclic Compounds, 4 or More Rings; D008565:Membrane Proteins; D000217:Acyltransferases; C491188:PORCN protein, human; D004950:Esterases; C000596390:Notum protein, human
keywords: Biomarker; Notum; PORCN inhibitor; Wnt signaling