Concurrent inhibition of TGF-β and mitogen driven signaling cascades in Dupuytren's disease - Non-surgical treatment strategies from a signaling point of view

We hypothesize that TGF-β-induced short-term activation of the MAPK pathway leads to an autonomous non-Smad driven fibrosis. Therefore, successful treatment strategies will target not only TGF-β/Smad, but also intracellular MAPK signaling. In this review we discuss possible scenarios in which such a drift from TGF-β induced Smad signaling to autonomous non-Smad signaling could be observed in DD. The potential therapeutic effects of small cytokine signaling cascades inhibitors, such as TGF-β type I receptor-, (pan-) tyrosine- or ERK1/2 MAP-kinase inhibitor will be highlighted. To abrogate the fibrotic trait and the recurrence of DD, we speculate on sequential and co-application of such molecules in order to provide possible new non-operative strategies for DD.