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Updated: Mar 26, 2026
Modeling Paracrine Noncanonical Wnt Signaling In Vitro
Published on: December 10, 2021
NOTUM is a potential pharmacodynamic biomarker of Wnt pathway inhibition
Babita Madan1, Zhiyuan Ke2, Zheng Deng Lei1
1Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore.
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.
Insights
Notum is identified as a novel biomarker for Wnt-driven cancers. Its blood levels may predict response to PORCN inhibitors and monitor treatment efficacy in cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Aberrant Wnt signaling, driven by overexpression or mutations, is implicated in numerous cancers.
- Inhibiting Porcupine (PORCN) enzyme activity blocks Wnt secretion and shows promise for treating cancers with elevated Wnt signaling.
- Lack of reliable biomarkers hinders prediction and monitoring of therapeutic response to upstream Wnt inhibitors.
Purpose of the Study:
- To identify novel biomarkers for Wnt-driven cancers.
- To evaluate Notum (NOTUM) as a potential biomarker for predicting and monitoring response to PORCN inhibitors.
- To investigate the utility of NOTUM and AXIN2 expression as predictive markers for PORCN inhibitor efficacy.
Main Methods:
- Analysis of gene expression patterns, focusing on NOTUM and AXIN2.
- Correlation studies between NOTUM levels and tumor growth.
- Assessment of NOTUM as a pharmacodynamic biomarker in blood.
Main Results:
- Notum (NOTUM) is identified as a potential biomarker for Wnt-driven cancers.
- Coordinated regulation of NOTUM and AXIN2 expression may predict response to PORCN inhibitors.
- NOTUM, a secreted protein, shows correlation with tumor growth and potential as a pharmacodynamic biomarker.
Conclusions:
- Notum represents a promising biomarker for Wnt-driven cancers.
- Combined NOTUM and AXIN2 expression analysis could guide treatment decisions for PORCN inhibitor therapy.
- NOTUM's presence in blood offers a valuable tool for monitoring therapeutic response to Wnt pathway inhibitors.
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