Bepler et al (2006) also reported that increased RRM1 expression resulted in resistance to gemcitabine both in vitro and clinically. They found that the gemcitabine IC50 of lung cancer cell lines with increased RRM1 expression was higher than that of cell lines with decreased RRM1 expression, and the results they obtained in a prospective phase II clinical trial in patients with advanced NSCLC showed a significant inverse correlation between RRM1 expression and disease response to gemcitabine and carboplatin therapy (P=0.002 and r=−0.498). This evidence concerns the gene RRM1 and lung cancer.