Heterogeneity in Tumors and Resistance to EGFR TKI Therapy-Response.
Heterogeneity in Tumors and Resistance to EGFR TKI Therapy-Response.
复制标题
肿瘤的异质性和对 EGFR TKI 治疗反应的耐药性。
DOI：
10.1158/0008-5472.can-16-0610
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发表时间：
2016
期刊：
影响因子：
11.2
通讯作者：
Shimamura,Takeshi
中科院分区：
文献类型：
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作者：
Shimamura,Takeshi
我们怀着极大的兴趣阅读了来自SUDA及同事的信(1)，这封信是关于我们最近发表的题为“EGFR突变的非小细胞肺癌导致对EGFR酪氨酸激酶抑制反应的分化耐药机制的肿瘤内异质性”的文章(2)。我们认为，他们的大多数担忧已经在马萨诸塞州波士顿马萨诸塞州总医院癌症中心的Jeffrey Engelman博士的实验室最近(2016年2月1日)的报告中得到了充分的解决，该报告展示了具有T790M EGFR酪氨酸激酶抑制剂(TKI)耐药性的EGFR突变的非小细胞肺癌(NSCLC)细胞在EGFR TKI治疗后如何演变(1)。我们还认为，使用已建立的人类细胞系模型，这封信中的一些观点超出了我们的文章的范围。以下是对这封信的逐点回应：1.CNG与T790M的流行。在这封信中，苏达和他的同事建议检查EGFR拷贝数增益(CNG)来估计带有T790M的次要克隆的流行率，这样我们就可以解释次要克隆如何在EGFR TKI治疗后成为显性抗性机制。这篇文章的目的是证明组织培养的非小细胞肺癌细胞由于细胞内的异质性而对治疗的反应不同。这篇文章的目的不是阐明轻微耐药克隆是如何在药物选择时进化的；然而，欢迎作者在他们自己的文章中研究这个问题。值得注意的是，Hata和他的同事最近使用患者来源的细胞系模型证明，EGFR T790M耐药非小细胞肺癌细胞既可以预先存在，也可以从耐药细胞进化(3)。我们认为，这份报告简明扼要地贬低了在EGFR TKI治疗之前估计T790M在亲代肿瘤中患病率的重要性。
We read with great interest the letter from Suda and colleagues (1) regarding our recent article titled" Intratumoral Heterogeneity in EGFR-Mutant NSCLC Results in Divergent Resistance Mechanisms in Response to EGFR Tyrosine Kinase Inhibition"(2). We believe that most of their concerns have already been adequately addressed in the recent (February 1, 2016) report from the laboratory of Dr. Jeffrey Engelman (Massachusetts General Hospital Cancer Center, Boston, MA), demonstrating how EGFR-mutant non–small cell lung carcinoma (NSCLC) cells with T790M EGFR tyrosine kinase inhibitor (TKI) resistance evolve upon EGFR TKI treatment (1). We also feel some of the points in the letter are beyond the scope of our article, using an established human cell line model. Following is a point-by-point response to the letter:1. CNG and prevalence of T790M. In the letter, Suda and colleagues suggest checking EGFR copy number gain (CNG) to estimate the prevalence of minor clones with T790M so that we could explain how the minor clone could emerge as a dominant resistant mechanism upon EGFR TKI treatment. The goal of this article is to demonstrate that tissue culture NSCLC cells respond differently to therapies due to the heterogeneity within the cells. It is not the goal of the article to elucidate how minor resistant clones evolve upon drug selection; however, the authors are welcome to investigate this issue in their own article. Of note, Hata and colleagues have recently demonstrated, using patient-derived cell line models, that EGFR T790M drug-resistant NSCLC cells can both preexist and evolve from drug-tolerant cells (3). We believe that this report succinctly devalues the importance of estimating the prevalence of T790M in parental tumors prior to the EGFR TKI treatment.