e20054 Background: Ribonucleotide reductase M1 (RRM1) is involved in regulation of cell proliferation and synthesis of deoxyribonucleotides for DNA. It is also a cellular target for gemcitabine (GEM) and overexpression of RRM1 was reported to be associated with the resistance to GEM. Though RRM1 expression has been reported as the biomarkers in predicting the response to chemotherapy clinically, the value of GEM remains inconsistent and controversial. Collagen gel droplet embedded culture-drug sensitivity test (CD-DST) is a newly developed in vitro chemosensitivity test that could directly inspect the anti-cancer drug sensitivity with fresh tumor tissue. With use of CD-DST test, we have verified the predictive value of RRM1 expression to the anti-cancer agent sensitivity for GEM in non-small cell lung cancer (NSCLC) tumor. Here, the predictive value of biomarker RRM1 to GEM was further verified with CD-DST. Methods: Twenty-five patients with primary NSCLC were used in this study. Expression of RRM1 was assessed by immunohistochemistry. For CD-DST test, viable cells were collected from fresh surgical specimen and embed into the collagen gel droplets in 3D condition. Tumor cells were exposed to GEM for 1 hour and further incubated with serum-free culture medium for 7 days. The in vitro sensitivity was expressed as the percentage T/C ratio, where T was the total volume of the treated group and C was the total volume of the control group. Results: 1)Anti-cancer drug sensitivity: The sensitivity for GEM (T/C%) was 76.2 ± 30.5. 2)Expression of biomarkers: RRM1 expression was 39.2 ± 28.2 %. 3) Correlation: The expression of RRM1 significantly correlated with drug sensitivity for GEM (r = 0.446, p = 0.0256). Higher expression of RRM1 indicated worse anti-cancer drug sensitivity for GEM. Conclusions: The significant correlation between the RRM1 expression and sensitivity to GEM was proved with CD-DST in NSCLC tumors. The expression of RRM1 may become a useful biomarker in predicting the drug sensitivity for GEM in NSCLC.
Development of an anti-cancer drug sensitivity test using a urine sample-derived organoid culture for dog bladder cancer