RRM1 Modulated In Vitro and In Vivo Efficacy of Gemcitabine and Platinum in Non–Small-Cell Lung Cancer

• DOI: 10.1200/jco.2006.06.1101
• Publication Date: 2006-09-12T00:46:58Z
• Authors: Gerold Bepler; Irina Kusmartseva; Swati Sharma; Ashish Gautam; Alan Cantor; Anupama Sharma; George Simon
• Keywords: Lung Neoplasms; Ribonucleoside Diphosphate Reductase; Reverse Transcriptase Polymerase Chain Reaction; Gene Expression Profiling; Tumor Suppressor Proteins; Endonucleases; Deoxycytidine; Survival Analysis; Gemcitabine; Carboplatin; 3. Good health; DNA-Binding Proteins; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Predictive Value of Tests; Carcinoma, Non-Small-Cell Lung; Antineoplastic Combined Chemotherapy Protocols; Tumor Cells, Cultured; Humans; Cisplatin

Purpose RRM1 encodes the regulatory subunit of ribonucleotide reductase and is a molecular target gemcitabine. Previous studies showed increased expression on continuous exposure cell lines to gemcitabine suggested improved survival for patients with low as opposed high tumoral when treated gemcitabine-containing chemotherapy. However, principal hypothesis that intratumoral levels gene are associated disease response has not been addressed. Patients Methods We constructed genetically modified lung cancer decreased investigate in vitro 50% inhibitory concentration (IC 50 ) gemcitabine, cisplatin, carboplatin. A prospective phase II clinical trial locally advanced non–small-cell was conducted pretreatment tumor collection determination ERCC1 by real-time reverse transcriptase polymerase chain reaction. The were correlated after two cycles Results In engineered 15-fold range, IC had 100-fold cisplatin carboplatin two-fold range. They highest constructs expression. trial, significantly (P = .002) inversely (r −0.498) response. similar trend .099). Conclusion results strongly suggest major predictor gemcitabine/platinum predictive albeit lesser degree.