Alternative efficacy-predicting markers for paclitaxel instead of CHFR in non-small-cell lung cancer

• Published in: Cancer biology & therapy 2010-11, Vol.10 (9), p.933-941
• Main Authors: Takeshita, Masafumi, Koga, Takaomi, Takayama, Koichi, Yano, Tokujiro, Maehara, Yoshihiko, Nakanishi, Yoichi, Sueishi, Katsuo
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - therapeutic use; Binding; Biology; Biomarkers, Tumor; Bioscience; Calcium; Cancer; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Cycle; DNA Methylation; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic - drug effects; Genes, erbB-1; Humans; Landes; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Mutation; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Organogenesis; Paclitaxel - therapeutic use; Poly-ADP-Ribose Binding Proteins; Polymerase Chain Reaction; Promoter Regions, Genetic; Proteins; Sequence Analysis, DNA; Smoking; Succinate Dehydrogenase - antagonists & inhibitors; Ubiquitin-Protein Ligases
• ISSN: 1538-4047; 1555-8576
• DOI: 10.4161/cbt.10.9.13320

Experiments using cancer cell lines have revealed that CHFR methylation correlates with sensitivity to microtubule inhibitors. However, this marker may not benefit actual clinical cases because it is difficult to detect CHFR methylation without surgically resected samples. Thus, a more easily accessible marker that correlates with sensitivity to microtubule inhibitors might be useful in NSCLC, especially in advanced cases. In this study, we show that EGFR gene status and smoking are predict the efficacy of treatment with microtubule inhibitors in NSCLC. Chemosensitivity to paclitaxel and six other chemotherapeutic agents was evaluated using the succinate dehydrogenase inhibition (SDI) method in 69 NSCLC cases, consisting of 48 adenocarcinomas, 20 squamous cell carcinomas and 1 large cell carcinoma. Next, we evaluated the relationships between CHFR or EGFR status and clinicopathologic data. Methylation-specific PCR (MSP) and direct DNA sequencing were performed to detect aberrant methylation of CHFR and EGFR mutations, respectively. CHFR gene promoter methylation and EGFR gene mutation were observed in 11 cases (15.9%) and 7 cases (10.1%), respectively. The SDI method revealed that CHFR gene methylation was significantly related to high sensitivity to paclitaxel (p