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

Masafumi Takeshita, Takaomi Koga, Koichi Takayama, Tokujiro Yano, Yoshihiko Maehara, Yoichi Nakanishi, Katsuo Sueishi

研究成果: ジャーナルへの寄稿学術誌査読

9 被引用数 (Scopus)


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<0.001), while no sensitivity was found to other agents. Interestingly, sensitivity to paclitaxel also correlated with wild type EGFR genotype (p=0.014) and patients with a smoking habit (0.029). Our results demonstrate that a wild-type EGFR genotype and a smoking habit, in addition to aberrant methylation of the CHFR gene, might be a predictor of clinical response to paclitaxel in NSCLC.

ジャーナルCancer Biology and Therapy
出版ステータス出版済み - 11月 1 2010

!!!All Science Journal Classification (ASJC) codes

  • 分子医療
  • 腫瘍学
  • 薬理学
  • 癌研究


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