Development of Small Molecules Targeting the Wnt Signaling Pathway in Cancer Stem Cells for the Treatment of Colorectal Cancer

Clin Colorectal Cancer. 2015 Sep;14(3):133-45. doi: 10.1016/j.clcc.2015.02.001. Epub 2015 Feb 17.

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.

Keywords: CRC; CSC; Chemotherapy; Targeted therapy; β-catenin.

Publication types

  • Review

MeSH terms

  • Adenomatous Polyposis Coli / genetics
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Drug Design
  • Humans
  • Molecular Targeted Therapy
  • Mutation
  • Neoplasm Recurrence, Local
  • Neoplastic Stem Cells / metabolism*
  • Wnt Signaling Pathway / drug effects
  • beta Catenin / genetics

Substances

  • Antineoplastic Agents
  • beta Catenin