Targeting the crosstalks of Wnt pathway with Hedgehog and Notch for cancer therapy.

Wnt pathway is an evolutionarily conserved signaling pathway determining patterning of animal embryos, cell fate, cell polarity, and a substantial role in the origin and maintenance of stem cells. It has been found to crosstalk with two other major developmental pathways, Hedgehog and Notch, in many embryological development cascades and in maintaining stemness of stem cells Research has shown that all the three pathways are potent in inducing tumorigenesis, driving tumor progression and aiding epithelial to mesenchymal transition in malignant cells, apart from maintaining cancer stem cells population inside the tumor tissue. Cancer stem cells are thought to aid in the process of tumor relapse, as they survive therapy by displaying drug resistance and then repopulating tumor tissues. Hence the role of these crosstalks in cancer is under intensive research. Inhibition of all the three pathways individually have resulted in tumor regression, but not optimally, as treatment failure and cancer relapse have been found to occur. Hence, instead of targeting a single pathway, targeting the crosstalk network could be a better alternative to conventional cancer treatment. Also, elimination of both tumor cells as well as cancer stem cells implies a reduced chance of relapse. Drugs developed to target these crosstalking networks, when used in combinatorial therapy, can potentially increase the efficacy of the therapy to a very large extent.