Department of Clinical Oncology, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, Japan.
J Cancer Res Clin Oncol. 2013 Aug;139(8):1391-6. doi: 10.1007/s00432-013-1454-9. Epub 2013 May 31.
The KRAS mutation has been associated with resistance to cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in metastatic colorectal cancer (mCRC). However, the predictive biomarkers of cetuximab resistance in KRAS wild-type mCRC remain unknown except BRAF, NRAS, and PIK3CA exon 20. The objective of the study is to study the impact of EGFR L2 mutations on resistance to cetuximab in KRAS wild-type patients.
A total of 247 mCRC patients were screened for KRAS status at the National Cancer Center Hospital between September 2008 and April 2010. We analyzed the EGFR L2 domain mutation status in KRAS wild type and in the patients treated with cetuximab-based therapy.
There were 136 patients with wild-type KRAS (55%). Sixty-five patients were analyzed for the L2 domain mutation status, and all patients received cetuximab-based therapy. One patient who had a mutation at exon 9 showed a partial response to cetuximab plus irinotecan.
Mutation of the EGFR L2 domain was analyzed in mCRC patients. Our findings do not provide sufficient evidence that EGFR L2 domain mutation is correlated with resistance to cetuximab.
KRAS 突变与转移性结直肠癌（mCRC）患者对西妥昔单抗（一种抗表皮生长因子受体[EGFR]的单克隆抗体）的耐药性相关。然而，除 BRAF、NRAS 和 PIK3CA 外显子 20 外，KRAS 野生型 mCRC 中对西妥昔单抗耐药的预测生物标志物仍未知。本研究旨在研究 EGFR L2 突变对 KRAS 野生型患者对西妥昔单抗耐药的影响。
2008 年 9 月至 2010 年 4 月，在国家癌症中心医院对 247 例 mCRC 患者进行了 KRAS 状态筛选。我们分析了 KRAS 野生型和接受西妥昔单抗治疗的患者中 EGFR L2 结构域突变状态。
有 136 例 KRAS 野生型（55%）患者。对 65 例患者进行了 L2 结构域突变状态分析，所有患者均接受了西妥昔单抗治疗。1 例 9 外显子突变患者对西妥昔单抗联合伊立替康有部分缓解。
对 mCRC 患者进行了 EGFR L2 结构域突变分析。我们的研究结果没有提供足够的证据表明 EGFR L2 结构域突变与西妥昔单抗耐药性相关。
