Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel gemcitabine

• Published in: British journal of cancer Vol. 98; no. 10; pp. 1710 - 1715
• Main Authors: Souglakos, J, Boukovinas, I, Taron, M, Mendez, P, Mavroudis, D, Tripaki, M, Hatzidaki, D, Koutsopoulos, A, Stathopoulos, E, Georgoulias, V, Rosell, R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.05.2008; Nature Publishing Group
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cancer Research; Clinical outcomes; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Docetaxel; Drug Resistance; Epidemiology; Female; Gene Expression Regulation, Neoplastic; Genetics and Genomics; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Male; Middle Aged; Molecular Medicine; Oncology; Predictive Value of Tests; Research Design; Ribonucleoside Diphosphate Reductase - genetics; Ribonucleoside Diphosphate Reductase - metabolism; Taxoids - administration & dosage; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; RRM1; gemcitabine; RRM2; pharmacogenomics; docetaxel; lung adenocarcinoma
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6604344

Ribonucleotide reductase subunits M1 (RRM1) and M2 (RRM2) are involved in the metabolism of gemcitabine (2′,2′-difluorodeoxycytidine), which is used for the treatment of nonsmall cell lung cancer. The mRNA expression of RRM1 and RRM2 in tumours from lung adenocarcinoma patients treated with docetaxel/gemcitabine was assessed and the results correlated with clinical outcome. RMM1 and RMM2 mRNA levels were determined by quantitative real-time PCR in primary tumours of previously untreated patients with advanced lung adenocarcinoma who were subsequently treated with docetaxel/gemcitabine. Amplification was successful in 42 (79%) of 53 enrolled patients. Low levels of RRM2 mRNA were associated with response to treatment ( P < 0.001). Patients with the lowest expression levels of RRM1 had a significantly longer time to progression ( P =0.044) and overall survival ( P =0.02) than patients with the highest levels. Patients with low levels of both RRM1 and RRM2 had a significantly higher response rate (60 vs 14.2%; P =0.049), time to progression (9.9 vs 2.3 months; P =0.003) and overall survival (15.4 vs 3.6; P =0.031) than patients with high levels of both RRM1 and RRM2. Ribonucleotide reductase subunit M1 and RRM2 mRNA expression in lung adenocarcinoma tumours is associated with clinical outcome to docetaxel/gemcitabine. Prospective studies are warranted to evaluate the role of these markers in tailoring chemotherapy.