Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.7157
Title: NOTUM is a potential pharmacodynamic biomarker of wnt pathway inhibition
Authors: Madan, B 
Ke, Z
Lei, Z.D 
Oliver, F.A 
Oshima, M
Lee, M.A
Rozen, S 
Virshup, D.M 
Keywords: AXIN2 protein
biological marker
esterase
Notum protein
unclassified drug
acyltransferase
axin
AXIN2 protein, human
esterase
ETC-159
fused heterocyclic rings
membrane protein
Notum protein, human
PORCN protein, human
tumor marker
animal experiment
animal model
Article
autocrine effect
blood analysis
controlled study
in vitro study
in vivo study
intracellular signaling
mouse
nonhuman
prediction
protein determination
protein expression
protein secretion
Wnt signaling pathway
animal
antagonists and inhibitors
Bagg albino mouse
biosynthesis
C57BL mouse
down regulation
drug effects
fibrosarcoma
genetic transfection
human
metabolism
nude mouse
pancreas tumor
tumor cell line
Wnt signaling
xenograft
Acyltransferases
Animals
Axin Protein
Biomarkers, Tumor
Cell Line, Tumor
Down-Regulation
Esterases
Fibrosarcoma
Heterocyclic Compounds, 4 or More Rings
Heterografts
Humans
Membrane Proteins
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Nude
Pancreatic Neoplasms
Transfection
Wnt Signaling Pathway
Issue Date: 2016
Publisher: Impact Journals LLC
Citation: Madan, B, Ke, Z, Lei, Z.D, Oliver, F.A, Oshima, M, Lee, M.A, Rozen, S, Virshup, D.M (2016). NOTUM is a potential pharmacodynamic biomarker of wnt pathway inhibition. Oncotarget 7 (11) : 12386-12392. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.7157
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.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/174984
ISSN: 19492553
DOI: 10.18632/oncotarget.7157
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