The Wnt Pathway: Emerging Anticancer Strategies

Aman      Gupta; Anukriti      Verma; Ashutosh      K. Mishra; Gulshan      Wadhwa; Sanjeev      K. Sharma; Chakresh      K. Jain

Abstract

The canonical Wnt cascade has emerged as a critical regulator of cancer cells. Activation of the Wnt signaling pathway has also been associated with stem cell, thus raising the possibility of its role in embryogenesis and in the proliferation of malignant cancer cells. Wnt pathway has been reported to be involved in normal physiological processes in adult animals and integrally associated with cancer cell growth and maintenance, thus has been harnessed to devise strategies for anticancer therapy. The presence or absence of some members in this pathway, such as β-catenin, Axin or APC, has been found to involve in different types of tumors in human beings. Dysregulation of the canonical Wnt/β-catenin signaling pathway, mostly by inactivating mutations of the APC tumor suppressor, or oncogenic mutations of β-catenin, has been implicated in colorectal tumorigenesis. Further, elevated levels of β-catenin protein, a hallmark of activated canonical Wnt pathway, have been significantly observed in common forms of human malignancies, indicating that activation of the Wnt pathway may play an important role in tumor development and hence could be a crucial consideration for drug development. The paper discusses the potential therapeutic and diagnostic strategies directing on Wnt pathways on the basis of recent patents and their analysis.

Keywords: Adenomatous polypolis coli (APC), AML, Axin, β-catenin, β-TrCP, Casein kinase 1α (CK1α), Dishevelled (Dsh), Frat1, GSK-3β (Glycogen synthase kinase 3β), PLC (phospholipase C), Wnt