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HER2 Mutations Predictive Value


European Society of Medical Oncology - March 15, 2016 评估不同类型癌症中不同HER2基因突变的预测值。 Assessing the predictive value of different HER2 mutations in different cancer types.

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Dr. Michail Ignatiadis, Attending Medical Oncologist, Jules Bordet Institute: My name is [Dr.] Michail Ignatiadis. I'm treating patients with breast cancer and the Jules Bordet Institute in Brussels in Belgium. Today, we will focus on the emerging topic of HER2 mutations (HER2m) in breast cancer. HER2 genomic aberrations, including HER2 mutations, have been observed in more than 25 tumor types. HER2 mutations and amplifications are mutually exclusive in more than 90% of the cases. These mutations have been detected using newer technologies such as next-generation sequencing. HER2 mutations in solid tumors are clustered within hotspots, either in the extracellular or in the kinase domain of the HER2 receptor. The frequency of specific HER2 mutations is associated with the site of cancer. As you can see in the highlighted examples of breast and lung cancer. So, what we have learned from preclinical models: Do HER2 mutations predict for sensitivity to anti-HER2 targeted agents in breast cancer? Investigators from Washington University demonstrated using functional studies that seven out of 13 HER2 mutations tested were activating mutations. Based on cell growth inhibition, they showed that all seven HER2-activating mutations were sensitive to neratinib (HKI-272) [Pfizer] , whereas lapatinib (Tykerb) [GSK] was less potent. A limitation of the above preclinical models is that the retroviral transduction of HER2 mutations that was used to produce these mutant cell lines does produce a lot of copies of HER2 mutation, which does not accurately reflect what is happening in patients' tumors. Investigators from Johns Hopkins [Cancer Center] have challenged the notion that HER2 mutations predict for sensitivity to anti-HER2 targeted agents. They have studied the functional consequences of seven HER2 mutations using an isogenic panel of HER2-mutant knock-in human breast epithelial cell lines. These cell lines have been produced using gene editing. Intriguingly, the majority of HER2 mutations did not induce oncogenic changes, and did not predict for sensitivity or resistance to neratinib [Pfizer] or lapatinib (Tykerb) [GSK] in these cell lines. But beyond preclinical models, what is the evidence from clinical studies of the value of HER2 mutations to predict for sensitivity to anti-HER2 targeted agents? There have been already several case reports from patients with tumors with HER2 mutations that have responded to anti-HER2 targeted agents, either alone or in combination. During the last San Antonio Breast Cancer Symposium (SABCS), preliminary data suggested encouraging activity of neratinib monotherapy, but more importantly, of the combination of neratinib plus fulvestrant (Faslodex) [AZN] in patients with HER2 non-amplified but HER2-mutant metastatic breast cancer. Here you see a patient that has responded to this combination after progressing on prior fulvestrant. Ongoing clinical studies aiming to enroll more than 500 patients with various solid tumors and HER2 mutations are exploring the activity of anti-HER2 targeted agents in this setting. These studies will address two critical questions: Can we use HER2 mutations to select patients for treatment with anti-HER2 targeted agents alone or in combination? And, what is the predictive value of different HER2 mutations in different cancer types? HER2 mutations are just one example highlighting the challenges and opportunities when genomics move to the clinics for precision medicine. I believe there will be more such examples in the near future, and this is exciting for our patients.

  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    aberration 畸变【名词】1. 偏差,越轨,错乱【法律】过失; 2. 失常【生物学】畸变,变型; 3. 【物理学】像差;【天文学】光行差
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    accurately reflect 精确地反映
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    activated 激活【及物动词】1. 使活动,开动,起动,触发;创设,成立(机构等); 2. 【化学】激活;活化; 3. 【物理学】赋能;使产生放射性; 4. 使(阴沟)产生微生物(而加以净化)
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    activating mutation 活化性突变
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    after progressing on prior fulvestrant 在起初使用氟维司群(fulvestrant)肿瘤进展后
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    alone or in combination 单独或组合
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    amplification 扩增; 放大; 增幅
  • amplify 扩增;放大
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    breast 乳腺癌【名词】1. 乳房;(比喻)营养的来源; 2. 胸;胸脯,胸膛;胸口;胸怀,心情; 3. (山)腹;(衣服的)胸部; 4. (扶拦、梁等的)下侧;(器物的)侧面;窗腰,窗下墙;炉胸;【矿物】工作面;【造船】中央系索
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    breast cancer 乳腺癌◆【略】BRCA
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    breast cancer patient 乳腺癌患者◆【略】BRCA
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    Breast Cancer Symposium 乳腺癌研讨会◆【略】BRCA
  • breast epithelial cell 乳腺上皮细胞
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    cancer 癌症【名词】1. 癌症;癌(瘤),肿瘤; 2. 弊病;社会恶习; 3. (the C-)【天文学】巨蟹座;巨蟹宫
  • cancer center 癌症中心
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    cancer type 癌症类型
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    case report  病例报道;个案报告;案例汇编
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    cell 细胞【名词】单元格,电池,牢房,单元,胞,手机,小区
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    cell growth 细胞生长
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    cell growth inhibition 细胞生长抑制
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    cell line 细胞系
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    clinic 诊所【名词】1. 临床讲授;临床实习课; 2. 诊所;门诊部; 3. 特殊病例分析;会诊
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    clinical 临床【形容词】疗效,临床医学
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    clinical study 临床研究
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    cluster 群集【名词】1. 丛集;丛;(葡萄等的)串,挂;(花)团;(秧)蔸;组; 2. (蜂、人等的)丛,群,群集; 3. 【物理学】聚集,组件;【化学】类族,基;(原子)团;【天文学】星团; 4. 【美军】(表示又一个同等勋章的)金属片; 5. 【语音】音丛,音群,义丛,词组; 6. 集中建筑群(在一大片土地上集中兴建住宅,以提供较大的公共休息场所); 【不及物动词, 及物动词】(使)成群;(使)群集
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    clustered within hotspots 聚集在突变热点内
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    combination 组合【名词】1. 结合,组合; 联合,合并,复合 2. 团体,协会,联盟; 合作 3. 组合物;结合体,联合体 4. 【化学】化合(物); 【矿物】聚形; 【数学】组合;【语法】组合词
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    critical 【形容词】1.关键性的,决定性的 2. 危险的,危急的;严重的 3. 批判的,批评的 4. 吹毛求疵的;爱挑剔别人的 (of, about)【医学】危象的;极期的 【数,物】临界的
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    critical question 关键的问题
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    demonstrate 显示出【及物动词】演示,证明,展示,表明,论证,示范,表现出,展现
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    detect 检测【及物动词】1. 发觉,发现,看破; 2. 【化学】检定;【无线电】检波
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    either alone or in combination 无论是单独还是组合
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    emerge 出现【不及物动词】1. 出现,显露,现出; 2. (自困境等中)摆脱;脱颖而出; 3. 发生,暴露
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    emerging topic 新专题; 新话题
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    enroll 注册【及物动词】1. 把…记入名簿[清单、目录];登记,编入;使入会,使入学; 2. 使入伍,使服兵役
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    epithelial 上皮【形容词】粘膜上皮,表皮
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    epithelial cell 上皮细胞
  • epithelial cell line 上皮细胞系
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    evidence 【名词】1. 证据 2. 形迹;迹象 3. 【法律】证据,证人;证词 4.明显;显著; 【及物动词】1. 证明; 2. 显示
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    extracellular 细胞外的
  • Extracting Microarray Gene Expression Patterns and Identifying co-expressed Genes 提取微阵列基因表达模式和确认共表达基因◆【略】EPIG
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    frequency 频率【名词】1. 屡次,频仍,频繁; 2. (脉搏等的)次数,出现率;频度;【物理学】频率,周率
  • fulvestrant 氟维司群
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    functional 功能【形容词】1. 官能的,机能的; 2. 在起作用的;职务上的; 3. 【数学】函数的; 4. 【建筑】从使用的观点设计[构成]的; 5. 有多种用途的;可改变用途的; 6. 可使用的,可操作的
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    functional consequence 功能性结果
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    functional study 功能性研究
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    gene 基因【名词】【生物学】基因; dominant gene 显性基因
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    gene editing 基因编辑
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    generation 一代人【名词】1. 代(约30年),世代,时代;同时代的人; 2. 一代[一世]; 3. 生殖,生育;发生,产生; 4. 【数学】(面、体、线的)形成; 5. 完善化阶段,完善化方案,完善化的模型;发展阶段
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    genomic 基因组【形容词】
  • genomic aberration 基因组异常
  • growth inhibition 生长抑制
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    highlight 突出显示【及物动词】在…上投上强光;强调,使显著;【美剧】派给;当主角; 【名词】(画中受光最多的)明亮部份;(常 pl.)(演出等的)精彩场面,精彩节目;(报纸中等)特讯,要闻;要点
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    highlighted example 突出显示的范例
  • human breast 人体乳房; 人乳腺
  • human epidermal growth factor receptor 2 人表皮生长因子受体2;人类表皮生长因子受体2◆【略】HER2◆【同】erythroblastosis oncogene B2 gene (ERBB2)
  • human epidermal growth factor receptor 2 genomic aberration 人类表皮生长因子受体2基因组异常◆【略】HER2
  • human epidermal growth factor receptor 2 mutation 人类表皮生长因子受体2基因突变◆【略】HER2
  • human epidermal growth factor receptor 2 mutations and amplifications 人类表皮生长因子受体2基因突变和扩增◆【略】HER2
  • human epidermal growth factor receptor 2 non-amplified but human epidermal growth factor receptor 2-mutant metastatic breast cancer 人类表皮生长因子受体2基因无扩增但有突变的转移性乳腺癌◆【略】HER2 BRCA
  • human epidermal growth factor receptor 2 receptor 人类表皮生长因子受体2受体◆【略】HER2
  • human epidermal growth factor receptor 2-activating mutation 人类表皮生长因子受体2基因活化性突变◆【略】HER2
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    in the near future 在不远的将来
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    induce 诱导【不及物动词】1. 劝诱,诱导,敦促; 2. 引导,导致; 3. 【逻辑学】归纳; 4. 【电学】感应
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    inhibition 抑制【名词】1. 禁止,阻止; 2. 【心理学】压制,抑制(作用),心障; 3. 【英法】诉讼停止命令; 4. 【宗教】教权停止命令; 5. 【化学】抑制(作用)
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    institute 研究所【名词】1. 协会,学会;学院,专科大学;(学院附设的)研究所; 2. 讲习会;(短期)训练班; 3. 会址,院址,校址,所址; 4. 原则,规则,惯例; 5. (给初学者用的法律、医学等的)浅说,(公认的)基本原理; 【及物动词】1. 设,设立,制定; 2. 实行,创立,开始; 3. 任命,【宗教】授…以圣职
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    intriguing 有趣的
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    investigator 研究者,调查者,侦查员
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    isogenic 同基因
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    isogenic panel 等基因组合
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    Johns Hopkins Cancer Center 约翰斯霍普金斯凯莫(Johns Hopkins Kimmel)癌症中心
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    kinase 激酶【名词】【生物化学】激酶
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    kinase domain 激酶结构域
  • lapatinib 拉帕替尼◆【商品名】Tykerb◆【略】GW572016
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    less potent 效力较弱
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    limitation 限制【名词】1. 限制; 2. 界限;极限;限度;局限性;限制因素; 3.【法律】(诉讼)时效,有效期限
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    lining 衬砌【名词】衬里,内衬,衬砌结构,面料,衬板;【及物动词】衬,炉衬,衬套
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    lung 肺癌【名词】1. 肺脏,肺; 2. (无脊椎动物的)呼吸器官; 3. 辅助呼吸的装置
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    lung cancer 肺癌
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    majority 多数【名词】1. 大多数,过半数,大部分; 2. (选举)(多于对方全体票数的)多得票数 (cf. plurality)。; 3. 陆军少校的职位,少校级; 4. 成年;法定年龄
  • medical oncologist 肿瘤科医生
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    metastatic 转移【形容词】转移灶,转移瘤
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    metastatic breast cancer 转移性乳腺癌◆【略】MBC
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    monotherapy 单药治疗
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    mutant 突变体【形容词】突变,变种,变异,异形,诱变;【名词】突变株
  • mutant cell 突变细胞
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    mutant cell line 突变细胞系
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    mutation 突变【名词】1. 变化,变异,更换;【生物学】突变;突变种;【语言学】母音变化;【音乐】(提琴的)变换把位;变声;【法律】让受; 2. (人世的)浮沉,盛衰
  • mutation test 突变试验
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    mutually exclusive 互相排斥的
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    next generation 下一代; 新一代
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    next-generation sequencing 新一代测序技术◆【略】NGS
  • oncogenic 致瘤的; 瘤原性的
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    oncogenic change 致癌行变化
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    oncologist 肿瘤学家
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    ongoing clinical study 正在进行的临床研究
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    opportunity 机会【名词】机遇,契机,时机,良机,商机
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    panel 小组【名词】1. 面,板;【建筑】四分板,门窗材;(木工)线板; 2. 【法律】陪审员名单;全体陪审员; 3. 进行公开讨论会的小组;(大会中的)小组委员会;一组调查对象;典型调查; 4. 鞍褥,鞍垫;木架鞍; 5. (苏格兰语)【法律】刑事被告
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    potent 有效的; 强有力的【形容词】强效,有力,烈性,强有力,强力
  • precision 【名词】精确性; [数] 精密度; 严谨; 【形容词】精确的; 精密的
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    precision medicine 精准医学
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    preclinical 临床前的; 医学基础科学的
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    preclinical model 临床前模型
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    predict 【及物动词】预测; 预言;预示 【不及物动词】做出预言;作预料;预计
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    predict for sensitivity 预测敏感性
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    predictive 预测【形容词】预见性,预估,预报,预知
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    predictive value 预测值
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    preliminary 初步【形容词】1. 预备的;初步的,初级的; 2. 序言性的,绪言的
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    preliminary data 初步数据
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    prior 【形容词】1. (用作前置定[修饰]语)在前的;优先的; 2. (与 to 连用)在…之前 (opp. post-erior) 比…优先;【副词】居先,在前
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    questioning 1. 疑问;质问 2. 询问; 审问
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    receptor 受体;接受器;感觉器官
  • Sound e31a43d441998f862b764d17930467a5a23de45c433219259bed5eb42e3a7615
    reflect 反映【及物动词】反映出,体现,反射,反省,反思,折射出,反应
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    resistance 【名词】1. 阻力; 抵抗,反抗 2. 抵抗能力; (对疾病的)抵抗力;(物质的)耐力 3. 【电学】阻抗;电阻器
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    retroviral transduction 逆转录病毒转导
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    San Antonio [Texas] Breast Cancer Symposium 圣安东尼奥[德州]乳腺癌研讨会◆【略】BRCA
  • selected patient 选择性患者
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    sensitivity 灵敏度【名词】1. 敏感(性);感受性; 2. (仪器等的)灵敏性; 3.【摄影】感光度
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    sequence 【名词】1. 序列,顺序,相关的系列; 2.结局,续发事件; 3.【数学】数列,序列 【及物动词】使按顺序排列; 【生物化学】定序,确定…的顺序
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    setting 1. 设置; 设定; 安装 2. 环境;背景; 布置
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    solid tumor 实体肿瘤
  • specific human epidermal growth factor receptor 2 mutation frequency 特定人类表皮生长因子受体2基因突变的频率◆【略】HER2
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    symposium 专题讨论会【名词】研讨会,学术研讨会,座谈会,学术讨论会,讨论会
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    targeted agent 靶向药物
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    transduction 1.【遗传学】转导(作用) 2. 【物理学】能量转换;变频
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    treated patient 治疗的患者
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    treatment 【名词】1. 治疗;疗法;疗程 2. 对待;处理 3.评述
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    tumor 肿瘤;肿块;赘生物
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    tumor type 肿瘤类型
  • Tykerb Tykerb◆【通用名称】lapatinib (拉帕替尼)◆【略】GW572016
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    Washington 华盛顿 (特指华盛顿的政治圈)◆ Washington, D.C. (District of Columbia)
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    when genomics move to the clinics 当基因组学研究转移到临床
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