Second, the mechanisms of pemetrexed resistance conferred by upregulation of the FGF2-FGFR1 pathway might differ in each cancer cell line, with the induced alteration of cellular functions potentially dependent on the innate molecular features of lung cancer cells such as the presence or absence of EGFR mutation, which might in turn affect the function of downstream signaling molecules in the kinase pathways of these cells. This evidence concerns the gene FGF2 and cancer.