More specifically, the sustained activation of EGF and TGF-α/EGFR and TGF-β/TGF-βR cascades as well as the down-regulation or loss of PTEN and enhanced levels of inflammatory cytokines such as TNF-α during PC progression and after treatment initiation may result in the stimulation of PI3K/Akt/mTOR, NF-κB and/or MAPK signalling elements in PC cells [28, 34, 35, 42, 119, 201]. This evidence concerns the gene TNF and pachyonychia congenita.