Rahmani et al (2003b) demonstrated that inhibition of PI3K sensitised human leukaemia cells to various HDACIs. Interestingly, in this model HDACI treatment caused AKT activation and the cytotoxic sensitisation caused by HDACI/LY combination treatments were mediated through inactivation of MAPK, rather than AKT inhibition. In contrast, in our experimental model, inhibition of ERK activity following U0126 treatment in combination with vorinostat did not induce cell death. Also, in contrast to leukaemia cells, vorinostat did not cause activation of AKT in HNSCC cells in vitro or in vivo. This evidence concerns the gene AKT1 and leukemia.