title: Development of Small Molecules Targeting the Wnt Signaling Pathway in Cancer Stem Cells for the Treatment of Colorectal Cancer.
abstract: Colorectal cancer (CRC) was ranked third in morbidity and mortality in the United States in 2013. Although substantial progress has been made in surgical techniques and postoperative chemotherapy in recent years, the prognosis for colon cancer is still not satisfactory, mainly because of cancer recurrence and metastasis. The latest studies have shown that cancer stem cells (CSCs) play important roles in cancer recurrence and metastasis. Drugs that target CSCs might therefore have great therapeutic potential in prevention of cancer recurrence and metastasis. The wingless-int (Wnt) signaling pathway in CSCs has been suggested to play crucial roles in colorectal carcinogenesis, and has become a popular target for anti-CRC therapy. Dysregulation of the Wnt signaling pathway, mostly by inactivating mutations of the adenomatous polyposis coli tumor suppressor or oncogenic mutations of β-catenin, has been implicated as a key factor in colorectal tumorigenesis. Abnormal increases of β-catenin levels represents a common pathway in Wnt signaling activation and is also observed in other human malignancies. These findings highlight the importance of developing small-molecule drugs that target the Wnt pathway. Herein we provide an overview on the current development of small molecules that target the Wnt pathway in colorectal CSCs and discuss future research directions.
authors: Department of Radiotherapy, the PLA 309 Hospital, Beijing, China; BioChain (Beijing) Science and Technology, Inc, Beijing, China. Electronic address: songlele@sina.com.
authors: Lele
authors: L
authors: Song
authors: Department of Radiotherapy, the PLA 309 Hospital, Beijing, China. Electronic address: liyuemin224@sina.com.
authors: Yuemin
authors: Y
authors: Li
authors: Department of Nuclear Medicine, the PLA 309 Hospital, Beijing, China.
authors: Baoming
authors: B
authors: He
authors: Department of Gastroenterology, the PLA General Hospital, Beijing, China.
authors: Yuan
authors: Y
authors: Gong
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D051176:beta Catenin
keywords: CRC; CSC; Chemotherapy; Targeted therapy; β-catenin