表皮生长因子受体罕见亚型敏感突变阳性肺癌的精准治疗
精准治疗是将遗传和基因组的信息作为临床治疗出发点的治疗模式，表皮生长因子受体酪氨酸激酶抑制剂（EGFR－TKIs）精准治疗是肺癌精准治疗的重要组成部分。EGFR突变主要发生于18外显子至21外显子区域，45%左右为19外显子缺失（19del）突变，40%左右为21外显子L858R突变，这些突变被称为敏感突变。除19del、L858R和T790M突变外，其余突变为罕见突变，包括Ins19、Ins20、E709、G719、S768、L861和一些复合突变等。既往一些小样本的回顾性研究和个案报道显示，Ins19、L861、G719X和S768I多表现为敏感突变，而Ins20却常常提示对一代和二代EG...
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| Published in | 中华肿瘤杂志 Vol. 39; no. 12; pp. 881 - 884 |
|---|---|
| Main Author | |
| Format | Journal Article |
| Language | Chinese |
| Published |
100091 北京,解放军第三〇九医院呼吸内科%解放军总医院呼吸内科, 北京,100853
2017
100853 北京,解放军总医院呼吸内科 |
| Subjects | |
| Online Access | Get full text |
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| Abstract | 精准治疗是将遗传和基因组的信息作为临床治疗出发点的治疗模式，表皮生长因子受体酪氨酸激酶抑制剂（EGFR－TKIs）精准治疗是肺癌精准治疗的重要组成部分。EGFR突变主要发生于18外显子至21外显子区域，45%左右为19外显子缺失（19del）突变，40%左右为21外显子L858R突变，这些突变被称为敏感突变。除19del、L858R和T790M突变外，其余突变为罕见突变，包括Ins19、Ins20、E709、G719、S768、L861和一些复合突变等。既往一些小样本的回顾性研究和个案报道显示，Ins19、L861、G719X和S768I多表现为敏感突变，而Ins20却常常提示对一代和二代EGFR－TKIs的敏感性差，但一些个别类型对三代EGFR－TKIs显示出较高的敏感性。目前针对Ins20的靶向药物Ap32788已进入临床试验。复合突变患者接受EGFR－TKIs疗效与单一敏感突变患者相似。总体来说，罕见敏感突变患者接受EGFR－TKIs治疗的有效率和无进展生存时间与经典敏感突变患者相似或略低于经典敏感突变患者，但较EGFR野生型患者高；与第一代EGFR－TKIs比较，第二代EGFR－TKIs可能更适用于EGFR罕见敏感突变患者的治疗。 |
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| AbstractList | 精准治疗是将遗传和基因组的信息作为临床治疗出发点的治疗模式，表皮生长因子受体酪氨酸激酶抑制剂（EGFR－TKIs）精准治疗是肺癌精准治疗的重要组成部分。EGFR突变主要发生于18外显子至21外显子区域，45%左右为19外显子缺失（19del）突变，40%左右为21外显子L858R突变，这些突变被称为敏感突变。除19del、L858R和T790M突变外，其余突变为罕见突变，包括Ins19、Ins20、E709、G719、S768、L861和一些复合突变等。既往一些小样本的回顾性研究和个案报道显示，Ins19、L861、G719X和S768I多表现为敏感突变，而Ins20却常常提示对一代和二代EGFR－TKIs的敏感性差，但一些个别类型对三代EGFR－TKIs显示出较高的敏感性。目前针对Ins20的靶向药物Ap32788已进入临床试验。复合突变患者接受EGFR－TKIs疗效与单一敏感突变患者相似。总体来说，罕见敏感突变患者接受EGFR－TKIs治疗的有效率和无进展生存时间与经典敏感突变患者相似或略低于经典敏感突变患者，但较EGFR野生型患者高；与第一代EGFR－TKIs比较，第二代EGFR－TKIs可能更适用于EGFR罕见敏感突变患者的治疗。 精准治疗是将遗传和基因组的信息作为临床治疗出发点的治疗模式,表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)精准治疗是肺癌精准治疗的重要组成部分.EGFR突变主要发生于18外显子至21外显子区域,45％左右为19外显子缺失(19del)突变,40％左右为21外显子L858R突变,这些突变被称为敏感突变.除19del、L858R和T790M突变外,其余突变为罕见突变,包括Ins19、Ins20、E709、G719、S768、L861和一些复合突变等.既往一些小样本的回顾性研究和个案报道显示,Ins19、L861、G719X和S768I多表现为敏感突变,而Ins20却常常提示对一代和二代EGFR-TKIs的敏感性差,但一些个别类型对三代EGFR-TKIs显示出较高的敏感性.目前针对Ins20的靶向药物Ap32788已进入临床试验.复合突变患者接受EGFR-TKIs疗效与单一敏感突变患者相似.总体来说,罕见敏感突变患者接受EGFR-TKIs治疗的有效率和无进展生存时间与经典敏感突变患者相似或略低于经典敏感突变患者,但较EGFR野生型患者高;与第一代EGFR-TKIs比较,第二代EGFR-TKIs可能更适用于EGFR罕见敏感突变患者的治疗. |
| Abstract_FL | Precise medicine is an emerging clinical therapeutic concept based on genomic and genetic information of patients. Epidermal growth factor receptor tyrosine kinase inhibitors ( EGFR-TKIs) is an important component of precise therapy for lung cancer patients. EGFR mutations occur mainly in exon 18 to 21, in which exon 19 deletion and exon 21 L858R point mutation that are known as sensitive mutations account for nearly 45％ and 40％, respectively. Except for the above two mutations and T790M point mutation, the rest are rare mutations, including Ins19, Ins20, E709, G719, S768, L861 and some compound mutations. Some previous retrospective studies of small sample size and case reports showed that most of EGFR exon19 (Ins), exon 21 (L861), exon 18 (G719X) and exon20 (S768I) mutations were sensitive to TKIs. And although the exon 20 insertion mutation is usually predicted to the first and second generations of EGFR-TKIs resistance, some specific types are sensitive to the third generation of EGFR-TKIs. Currently, targeted drugs for Ins20 -Ap32788 mutation has entered into clinical trials. Patients with complex mutations have similar efficacy on EGFR-TKIs in comparison with those with single sensitivity mutations. In conclusion, when patients with rare sensitive mutations received EGFR-TKIs therapy, the efficacy and progression-free survival time is similar to or slightly lower than those with classical sensitive mutations, whereas it is higher than those with wild-type EGFR. Compared with the first generation of EGFR-TKIs, second generation EGFR-TKIs may be more suitable for the treatment of lung cancer patients harboring rare sensitive EGFR mutations. |
| Author | 李芸;陈良安 |
| AuthorAffiliation | 解放军总医院呼吸内科,北京100853 |
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| Author_FL | Chen Liang′an Li Yun |
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| Author_xml | – sequence: 1 fullname: 李芸;陈良安 |
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| Keywords | 精准治疗 Tyrosine kinase inhibitor 酪氨酸激酶抑制剂 Rare sensitive mutation 肺肿瘤 表皮生长因子受体 罕见敏感突变 Precise therapy Epidermal growth factor receptor Lung neoplasms |
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| Notes | Lung neoplasms; Precise therapy; Epidermal growth factor receptor; Rare sensitive mutation; Tyrosine kinase inhibitor Precise medicine is an emerging clinical therapeutic concept based on genomic and genetic information of patients. Epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKIs） is an important component of precise therapy for lung cancer patients. EGFR mutations occur mainly in exon 18 to 21, in which exon 19 deletion and exon 21 L858R point mutation that are known as sensitive mutations account for nearly 45% and 40%, respectively. Except for the above two mutations and T790M point mutation, the rest are rare mutations, including Ins19, Ins20, E709, G719, S768, L861 and some compound mutations. Some previous retrospective studies of small sample size and case reports showed that most of EGFR exon19 （Ins）, exon 21 （L861）, exon 18 （G719X） and exon20 （S768I） mutations were sensitive to TKIs. And although the exon 20 insertion mutation is usually predicted to the first and second generat |
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| PublicationTitle | 中华肿瘤杂志 |
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| PublicationYear | 2017 |
| Publisher | 100091 北京,解放军第三〇九医院呼吸内科%解放军总医院呼吸内科, 北京,100853 100853 北京,解放军总医院呼吸内科 |
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| SubjectTerms | 精准治疗 罕见敏感突变 肺肿瘤 表皮生长因子受体 酪氨酸激酶抑制剂 |
| Title | 表皮生长因子受体罕见亚型敏感突变阳性肺癌的精准治疗 |
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