Therapeutic Potential of Afatinib for Cancers with ERBB2 (HER2) Transmembrane Domain Mutations G660D and V659E.
Therapeutic Potential of Afatinib for Cancers with ERBB2 (HER2) Transmembrane Domain Mutations G660D and V659E.
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DOI：
10.1634/theoncologist.2017-0345
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发表时间：
2018-02
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通讯作者：
H. Yamamoto;S. Toyooka;T. Ninomiya;S. Matsumoto;M. Kanai;S. Tomida;K. Kiura;M. Muto;K. Suzawa
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作者：
H. Yamamoto;S. Toyooka;T. Ninomiya;S. Matsumoto;M. Kanai;S. Tomida;K. Kiura;M. Muto;K. Suzawa
我们以前报道过一个遗传性肺癌家族，其中禽成红细胞白血病病毒癌基因同源物2（erb-b2受体酪氨酸激酶2）（ERBB 2;人表皮生长因子受体2 [HER 2]）跨膜结构域（G660 D）的种系突变似乎是癌症易感性的原因。尽管关于治疗的数据很少，但抗ERBB 2治疗剂可能对ERBB 2突变型癌症有效。作者所在研究所的家族性肺癌患者发生骨转移伴肺肿瘤增大，并接受ERBB 2抑制剂阿法替尼治疗。我们还在作者的另一个研究所遇到了一名壶腹腺癌患者，该患者具有ERBB 2 G660 D和S310 F突变，这是通过全面的基因组分析揭示的。该患者随后接受阿法替尼治疗，也获得了一过性缓解。我们还在PubMed、癌症基因组图谱（TCGA）和纪念斯隆-凯特琳癌症靶点综合突变谱（MSK-IMPACT）数据库中搜索了各种类型癌症中的ERBB 2跨膜突变。除了我们的两个病例，通过PubMed发现了两例V659 E突变患者。TCGA中发现3例潜在患者。此外，MSK-IMPACT允许鉴定另外三种具有G660 D突变的尿路上皮癌和两种具有V659 E突变的肺腺癌。我们的经验表明，建立一个关于复发但不太常见突变患者的临床基因组和治疗结果的综合信息数据库对于实施精确肿瘤学至关重要。关键点罕见但可靶向的突变，如禽成红细胞白血病病毒癌基因同源物2（erb-b2受体酪氨酸激酶2）（ERBB2;人表皮生长因子受体2 [HER 2]）跨膜结构域（TMD）突变可以通过全面的基因组分析来检测。阿法替尼可能对ERBB 2（HER 2）TMD突变的癌症患者有效。为了实施精确的肿瘤治疗，必须建立一个关于复发但不太常见的突变患者的临床基因组和治疗结果的综合信息数据库。
We previously reported on a family with hereditary lung cancer, in which a germline mutation in the transmembrane domain (G660D) of avian erythroblastic leukemia viral oncogene homolog 2 (erb-b2 receptor tyrosine kinase 2) (ERBB2; human epidermal growth factor receptor 2 [HER2]) seemed to be responsible for the cancer predisposition. Although few data are available on treatment, anti-ERBB2 therapeutic agents may be effective for ERBB2-mutant cancers. The familial lung cancer patient in one of the authors' institutes developed bone metastasis with enlarging lung tumors and was treated with the ERBB2 inhibitor afatinib. We also encountered a patient with ampullary adenocarcinoma with ERBB2 G660D and S310F comutations in another institute of the authors', revealed by comprehensive genomic profiling. This patient was then treated with afatinib and also achieved transitory response. We also searched for ERBB2 transmembrane mutations in various types of cancers in PubMed, The Cancer Genome Atlas (TCGA), and the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) database. Besides our two cases, two patients with V659E mutations were found via PubMed. Three potential patients were found in TCGA. In addition, MSK-IMPACT allowed identification of three additional urothelial carcinomas with G660D mutations and two lung adenocarcinomas with V659E mutations. Our experience suggests that establishing a database of integrated information regarding the clinical genome and therapeutic outcome of patients with recurrent but less common mutations is essential to implement precision oncology. KEY POINTS Rare but targetable mutations such as avian erythroblastic leukemia viral oncogene homolog 2 (erb-b2 receptor tyrosine kinase 2) (ERBB2; human epidermal growth factor receptor 2 [HER2]) transmembrane domain (TMD) mutations can be detected by comprehensive genomic profiling.Afatinib may be effective for patients with cancer with ERBB2 (HER2) TMD mutations.In order to implement precision oncology, it is important to establish a database of integrated information regarding the clinical genomes and therapeutic outcomes of patients with recurrent but less common mutations.