“…Epigenetic inactivation of WNT signaling antagonists such as the SFRP genes is not restricted to cSCC, but rather is detected in a variety of other types of SCC tumours, including oral (Paluszczak, et al 2015;Pannone, et al 2010;Sogabe, et al 2008), oesphageal (Kishino, et al 2016;Liu, et al 2011;Meng, et al 2011;Saito, et al 2014;Yang, et al 2012), cervical (Delmas, et al 2011;Siegel, et al 2015) and head & neck (HN) SCCs (Marsit, et al 2006), and thus could represent a universal mechanism of WNT activation in SCC tumours. LGK974, is well-tollerated, potent and highly efficatious in human HNSCC cells (Liu, et al 2013), suggesting it may prove a lead therapeutic in other SCCs where WNT/β-catenin signaling drives carcinogenesis. Consistent with this is the interesting finding that another Porcupine inhibitor, IWP2, can induce tumour regression in chemically induced murine keratoacanthomas (a HF-derived benign variant of cSCC), which highlights WNT/β-catenin signaling as a key regulator to sustain cutaneous tumour growth (Zito, et al 2014).…”