Targeting the Wnt Pathway in Cancer: A Review of Novel Therapeutics

Abstract

Wnt signaling is an evolutionarily conserved pathway that controls cell-to-cell interactions during embryogenesis. In adults, Wnt signaling plays a role in tissue homeostasis in almost every organ system. Aberrations within this pathway are implicated in a spectrum of human diseases. A variety of perturbations have been described in both solid and hematologic malignancies, lending way to Wnt signaling as a target for anti-cancer therapy. Of particular interest is the role of Wnt signaling in the development and maintenance of cancer stem cells, a rare population of cells that are able to maintain a tumor via self-renewal and thought to be more resistant to chemotherapy than bulk tumor cells. The ability to eradicate cancer stem cells may decrease the risk of cancer relapse and metastasis. A number of therapeutic agents specifically targeting the Wnt pathway have entered clinical trials, either as monotherapy or in combination with chemotherapy. We will provide an overview of agents that have been developed to target the Wnt pathways and a summary of pre-clinical and clinical trials.

RETRACTED ARTICLE: MicroRNA-93-5p promotes epithelial-mesenchymal transition in gastric cancer by repressing tumor suppressor AHNAK expression

“…β-catenin can function in the cell-cell adhesion and in signal transduction, but can also act in conjunction with E-cadherin to form adherent junctions between epithelial cells [28]. Wnt signaling pathway plays a key role in cell proliferation, differentiation as well as migration [29]. It is also documented that Wnt signaling pathway also known as Wnt/β-catenin signaling pathway since it can regulate β-catenin protein levels therefore activating the Wnt, which could regulate Frizzled-1/β-catenin signaling pathway [30].…”

An update of Wnt signalling in endometrial cancer and its potential as a therapeutic target

“…It is also one of the most extensively studied in cancer and has been implicated in majority of human malignancies, including endometrial tumours (Anastas & Moon 2012, Dellinger et al 2012, van der Zee et al 2013, Anastas 2015, Eskander et al 2016. Wnt signalling mechanisms in the context of cancer have been extensively reviewed (Anastas & Moon 2012, Niehrs 2012, Humphries & Mlodzik 2017, Kim et al 2017, Schatoff et al 2017, Tabatabai et al 2017, Zhan et al 2017.…”

Gene Expression Comparison Between the Lymph Node-Positive and Negative Reveals a Peculiar Immune-microenvironment Signature and a Theranostic Role for WNT Targeting in Pancreatic Ductal Adenocarcinoma: A Pilot Study

“…Interestingly, our bioinformatic analysis revealed WNT2 and WNT pathway, well described drivers of invasiveness, epithelial mesenchymal transition, drug-resistance and metastatic potential [25][26][27][28], as a significant signature enriched in N pos patient group. Therefore, we investigated whether Peer-reviewed version available at Cancers 2019, 11, 942; doi:10.3390/cancers11070942 of a tool to circumvent the pro-tumour M2 addicted immune suppressive-environment [44].…”