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非小细胞肺癌(NSCLC)患者接受酪氨酸激酶抑制剂治疗后出现 EGFR 和 KRAS 基因突变的多样性。

Multiplicity of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitors.

机构信息

Laboratory for Molecular Genetics and Oncology, Genomac International, Ltd., Prague, Czech Republic.

出版信息

Anticancer Res. 2010 May;30(5):1667-71.

Abstract

BACKGROUND

Concurrent presence of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC) patients is relatively rare and their appearance is believed to be mutually exclusive. Tumours harbouring KRAS mutation are perceived as not being capable of response to tyrosine kinase inhibitor (TKI) therapy.

PATIENTS AND METHODS

This paper presents 5 case reports of patients with tumours harbouring multiple EGFR and/or KRAS mutations. There were 3 patients with EGFR mutations (2 x exon 19 deletions, 1 x L858R) combined with KRAS mutations (2 x Gly12Asp, 1 x Gly12Val), 1 patient with two EGFR mutations (exon 19 deletion + L858R) and 1 patient with two KRAS mutations (Ala11Pro + Gly12Val).

RESULTS

All EGFR(+)/KRAS(+) patients had initially showed positive response to TKI treatment. The EGFR(+)/EGFR(+) patient has exhibited strong rash and good response with the best survival, while the KRAS(+)/KRAS(+) patient did not respond to TKI therapy.

CONCLUSION

EGFR(+)/KRAS(+) combination does not necessarily pose a negative prediction. This is probably due to the multiclonal character of the tumour displaying partial response in the EGFR(+) subpopulation.

摘要

背景

非小细胞肺癌(NSCLC)患者同时存在 EGFR 和 KRAS 突变的情况相对较少,且两者被认为是相互排斥的。携带 KRAS 突变的肿瘤被认为不能对酪氨酸激酶抑制剂(TKI)治疗产生反应。

患者和方法

本文报告了 5 例同时存在多种 EGFR 和/或 KRAS 突变的患者。其中 3 例存在 EGFR 突变(2 例外显子 19 缺失,1 例 L858R)和 KRAS 突变(2 例 Gly12Asp,1 例 Gly12Val),1 例存在两个 EGFR 突变(外显子 19 缺失+L858R),1 例存在两个 KRAS 突变(Ala11Pro+Gly12Val)。

结果

所有 EGFR(+)/KRAS(+) 患者最初均对 TKI 治疗有阳性反应。EGFR(+)/EGFR(+) 患者表现出强烈的皮疹和良好的反应,生存最佳,而 KRAS(+)/KRAS(+) 患者对 TKI 治疗无反应。

结论

EGFR(+)/KRAS(+) 组合不一定预示着负面结果。这可能是由于肿瘤的多克隆特征导致 EGFR(+)亚群出现部分反应。

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