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Targeting Notch Signaling in Colorectal Cancer
Suman Suman1, Trinath P Das1, Murali K Ankem1
1Department of Urology, University of Louisville, Louisville, KY 40202.
Abstract:
The activation of Notch signaling is implicated in tumorigenesis in the colon due to the induction of pro-survival signaling in colonic epithelial cells. Chemoresistance is a major obstacle for treatment and for the complete eradication of colorectal cancer (CRC), hence, the inhibition of Notch is an attractive target for CRC and several groups are working to identify small molecules or monoclonal antibodies that inhibit Notch or its downstream events; however, toxicity profiles in normal cells and organs often impede the clinical translation of these molecules. Dietary agents have gained momentum for targeting several pro-survival signaling cascades, and recent studies demonstrated that agents that inhibit Notch signaling result in growth inhibition in preclinical models of CRC. In this review, we focus on the importance of Notch as a preventive and therapeutic target for colon cancer and on the effect of WA on this signaling pathway in the context of colon cancer.
Insights
Notch signaling promotes colon cancer survival and chemoresistance. Inhibiting Notch, potentially with dietary agents like Withaferin (WA), shows promise for colon cancer prevention and therapy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Signaling
Background:
- Notch signaling activation promotes colon tumorigenesis by enhancing pro-survival pathways in colonic epithelial cells.
- Chemoresistance in colorectal cancer (CRC) presents a significant challenge, making Notch inhibition an attractive therapeutic strategy.
- Clinical translation of Notch inhibitors is hindered by toxicity in normal cells and organs.
Purpose of the Study:
- To review the role of Notch signaling as a preventive and therapeutic target in colon cancer.
- To examine the impact of Withaferin (WA) on Notch signaling in the context of colon cancer.
Main Methods:
- Literature review focusing on Notch signaling in colon cancer.
- Analysis of preclinical data on dietary agents targeting Notch.
- Discussion of WA's effect on the Notch pathway in colon cancer models.
Main Results:
- Notch signaling contributes to colon cancer cell survival and chemoresistance.
- Dietary agents inhibiting Notch signaling demonstrate growth inhibition in preclinical CRC models.
- WA emerges as a potential agent affecting Notch signaling in colon cancer.
Conclusions:
- Notch signaling is a critical target for colon cancer prevention and therapy.
- Dietary agents like WA offer a promising avenue for inhibiting Notch and treating colon cancer with potentially reduced toxicity.
- Further research into WA's mechanism and clinical efficacy in colon cancer is warranted.
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