Targeting Notch Signaling in Colorectal Cancer.
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.
Department of Urology, University of Louisville, Louisville, KY 40202.
Suman
S
Suman
Department of Urology, University of Louisville, Louisville, KY 40202.
Trinath P
TP
Das
Department of Urology, University of Louisville, Louisville, KY 40202.
Murali K
MK
Ankem
Department of Urology, University of Louisville, Louisville, KY 40202.
Chendil
C
Damodaran
Notch-1; chemoresistance; colon cancer; dietary agent; prevention; treatment