목적: The MEK-ERK pathway is up-regulated in oral squamous cell cancer (OSCC). Thus, molecular targeting of this critical mitogenic pathway may have therapeutic potential for the treatment of OSCC however, chemoresistance to long-term therapy may develop, which is a major cause of cancer treatment failure and leads to a reduction in the survival rate of cancer patients. We aimed to investigate the cause of the limited therapeutic effect of MEK inhibitor in OSCC because ERK rebound has been shown after MEK inhibition inevitably occurs. 방법:Receptor tyrosine kinase signaling array was used to find out screening possible bypassing signal of MEK inhibition (AZD6244). FGF-FGFR3 pathway activation with ERK rebound after MEK inhibition was revealed by western blot, real time PCR, and ELISA. Inhibition study was done using FGFR3 inhibitor (PD173074) and siRNA. Then, we confirmed in vitro results by using orthotopic xenograft mouse model. 결과:Activation of FGFR3 was accompanied with rebound ERK and activation of AKT signal in OSCC after AZD6244 treatment. Down-regulation of FGF2 and FGFR3 repressed ERK rebound as well as FGFR3 activation and resulted in apoptotic cell death and tumor regression. 결론:ERK rebound and thereby resistance of AZD6244 inhibited by down regulation of FGFR3 signal which was activated by AZD6244 treatment, suggesting that FGFR pathway could be salvage signal against MEK inhibition and combination of FGFR3 inhibitor with MEK inhibitor may be a potential therapeutic option to overcome resistance for the MEK targeting drugs.