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

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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.

元の言語英語
ページ(範囲)933-941
ページ数9
ジャーナルCancer Biology and Therapy
10
発行部数9
DOI
出版物ステータス出版済み - 11 1 2010

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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    Takeshita, M., Koga, T., Takayama, K., Yano, T., Maehara, Y., Nakanishi, Y., & Sueishi, K. (2010). Alternative efficacy-predicting markers for paclitaxel instead of CHFR in non-small cell lung cancer. Cancer Biology and Therapy, 10(9), 933-941. https://doi.org/10.4161/cbt.10.9.13320