Adaptive drug resistance, whereby tumor cells develop mechanisms to resist the anti-tumor effects of these pathway inhibitors, has emerged as a major reason for the failure of such approaches [98]; in a recent study Britschgi et al. (2012) proposed that the up-regulation of CXCL8 signaling, in a JAK-dependent manner, may be one such mechanism by which some cancer cells develop resistance to the PI3K inhibitor, BEZ235 [99]. The gene discussed is CXCL8; the disease is cancer.