Abstract
WNT signalling is known to be a crucial regulator of embryonic development and tissue homeostasis. Aberrant expression of WNT signalling elements or their mutations has been implicated in carcinogenesis and/or the progression of several different cancer types. Investigations of how WNT signalling affects carcinogenesis and cancer progression have revealed that it has essential roles in the regulation of proliferation, apoptosis, and cancer stemness and in angiogenesis and metastasis. Consequently, WNT-targeted therapy has gained much attention and has resulted in the development of several small molecules, the majority of which act as inhibitors of different WNT signalling events. However, although numerous inhibitory WNT signalling drug candidates have been included in clinical trials, no significant breakthroughs have been made. This could possibly be due to problems with inefficient binding to the target, compensatory signalling mechanisms and toxicity towards normal cells. Therapeutic peptides targeting WNT signalling in cancer cells have been developed as an alternative approach, with the hope that they might overcome the limitations reported for small WNT inhibitory molecules. In this chapter, we describe recent developments made in the design and characterization of WNT signalling-derived peptides aiming at their use as alternative cancer therapeutics and/or combined adjuvant therapy to conventional therapies.
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Acknowledgements
This work was supported by the Swedish Cancer Foundation, the Skåne University Hospital Research Foundation, Sweden, and the Governmental Funding of Clinical Research within the National Health Services (ALF; all to T.A.). This study was also supported by grants from the Royal Physiographic Society of Lund, Sweden (to V.Y., N.J. and L.M.).
Conflict of Interest
T.A. is a shareholder, scientific advisor, and member of the Board of WntResearch AB. This does not alter the author’s adherence to all given guidelines for publication. V.Y., N.J., and LM have no conflicts of interest to declare.
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Yadav, V., Jobe, N., Mehdawi, L., Andersson, T. (2021). Targeting Oncogenic WNT Signalling with WNT Signalling-Derived Peptides. In: Schulte, G., Kozielewicz, P. (eds) Pharmacology of the WNT Signaling System. Handbook of Experimental Pharmacology, vol 269. Springer, Cham. https://doi.org/10.1007/164_2021_528
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