Lung cancer in never smokers: a different disease
Lung cancer in never smokers: a different disease
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DOI：
10.1007/s13665-013-0071-z
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发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
T. Vavalà;M. Giaj Levra;S. Novello
中科院分区：
文献类型：
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作者：
T. Vavalà;M. Giaj Levra;S. Novello
从不吸烟者肺癌 (LCINS) 通常被认为是一种不同的疾病实体，具有不同的分子亚分类。值得注意的是，表皮生长因子受体（EGFR）、v-Ki-ras2 Kirsten 大鼠肉瘤病毒癌基因同源物（KRAS）和间变性淋巴瘤激酶（ALK）重排的可操作突变是 LCINS 中三个主要的复发性致癌改变。 HER2 和 BRAF 突变、ROS1 和 RET 重排也包括在内，尽管已知这些突变的发生频率较低。尽管未经选择的患者对 EGFR 酪氨酸激酶抑制剂 (TKI) 的总体缓解率 (ORR) 仅 10%，但亚组分析显示，女性、从不吸烟者和携带 EGFR 突变的亚洲人的缓解率和生存率相对较高，这表明吸烟状况对 EGFR 突变患者具有预测和/或预后意义。亚组之间 KRAS 突变患病率的差异也得到了描述：8% 的从不吸烟者与 57% 的前/当前吸烟者携带 KRAS 突变，尽管未选择的肺腺癌患者中有 3% 至 5% 存在 ALK 重排，但从不吸烟者的频率似乎更为明显。有人建议，KRAS 突变的预后和预测相关性因吸烟状况而异，但其特征仍然较少，ALK 重排和其他改变与吸烟相关的预后和预测价值仍然很大程度上未知。肺癌患者的临床试验应始终根据吸烟史进行分层，根据吸烟状况识别差异可能有助于优化未来的靶向治疗。
Lung cancer in never smokers (LCINS) is often considered a different disease entity with a distinct molecular sub-classification. Notably, actionable mutations in epidermal growth factor receptor (EGFR), v-Ki-ras2 Kirsten Rat sarcoma viral oncogene homolog (KRAS) and anaplastic lymphoma kinase (ALK)-rearrangement are three major recurrent oncogenic alterations in LCINS. HER2 and BRAF mutations, ROS1 and RET rearrangements are also included, although these are known to occur with low frequencies. Although the overall response rate (ORR) to EGFR tyrosine kinase inhibitors (TKIs) in unselected patients was only 10 %, subgroup analyses revealed comparatively higher response rates and survival in women, never smokers and Asians harbouring EGFR mutations, suggesting a predictive and/or prognostic significance among patients with mutated EGFR by smoking status. Differences in the prevalence of KRAS mutations between subgroups have also been described: 8 % of never smokers versus 57 % of former/current smokers with lung adenocarcinoma harbour KRAS mutations, and although 3 % to 5 % of unselected patients with lung adenocarcinoma have ALK rearrangements, the frequency appears to be more pronounced in never smokers. There is a suggestion that prognostic and predictive relevance of KRAS mutations varies by smoking status, but it is still less characterized as well as the smoking-related prognostic and predictive value of ALK rearrangement and the other alterations, which are still largely unknown. Clinical trials of lung cancer patients should always be stratified by smoking history and the identification of differences according to smoking status may help optimize future targeted therapies.