Suman Suman, Das Trinath P, Ankem Murali K, Damodaran Chendil
Department of Urology, University of Louisville, Louisville, KY 40202.
Curr Colorectal Cancer Rep. 2014 Dec 1;10(4):411-416. doi: 10.1007/s11888-014-0252-3.
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.
Notch信号的激活与结肠癌的肿瘤发生有关,因为它能诱导结肠上皮细胞中的促生存信号。化疗耐药是治疗和彻底根除结直肠癌(CRC)的主要障碍,因此,抑制Notch是CRC的一个有吸引力的靶点,几个研究小组正在努力寻找抑制Notch或其下游事件的小分子或单克隆抗体;然而,正常细胞和器官中的毒性特征常常阻碍这些分子的临床转化。膳食剂在靶向多个促生存信号级联方面已获得进展,最近的研究表明,抑制Notch信号的试剂在CRC临床前模型中导致生长抑制。在这篇综述中,我们聚焦于Notch作为结肠癌预防和治疗靶点的重要性,以及在结肠癌背景下白藜芦醇(WA)对该信号通路的影响。