Fig. 9.

Diagram depicting the proposed mechanism of action of sorafenib in mesothelioma TICs. Sorafenib treatment causes the inhibition of MEK and ERK1/2 phosphorylation and the downregulation of Mcl-1 expression, leading to cell cycle arrest and activation of the apoptotic program. Sorafenib antitumor effects are mainly ascribed to a direct inhibition of FGFR1 activity rather than downstream effectors, such as Raf/Ras/MEK/ERK pathway. Thus TIC cultures autocrinally activating FGFR1 via the release of high amount of bFGF are likely to be more sensitive to the drug. bFGF basic fibroblast growth factor, FGFR FGF receptor, TIC tumor-initiating cell