Genetic Characterization of Brain Metastases in the Era of Targeted Therapy.
Genetic Characterization of Brain Metastases in the Era of Targeted Therapy.
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DOI：
10.3389/fonc.2017.00230
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发表时间：
2017
影响因子：
4.7
通讯作者：
Brastianos PK
中科院分区：
文献类型：
--
作者：
Han CH;Brastianos PK
在当今分子靶向治疗和精确医学的时代，癌症治疗的选择越来越多地根据个人所患癌症的分子或基因组特征进行定制。此前，临床上对脑转移控制不足的观察被广泛归因于抗癌药物缺乏对中枢神经系统(CNS)的渗透。然而，最近的数据表明，这种观察结果是有遗传原因的。对脑转移瘤及其匹配的原发肿瘤和其他颅外转移瘤的基因组分析表明，脑转移瘤可能含有潜在的可操作的驱动程序突变，这些突变是它们所独有的。识别脑转移的特异性基因组改变和针对这些突变的靶向治疗是一个重要的研究领域，可能会改善脑转移患者的生存结果。基因组检测的新方法，如在脑脊液中使用无细胞循环肿瘤DNA(CtDNA)，有助于促进我们对脑转移瘤基因组学的理解，这对精确医学至关重要。脑脊液衍生的ctDNA测序对于不适合手术切除或有多发性脑转移瘤的患者可能特别有用，这些转移瘤可能含有与原发肿瘤不同的突变。与传统的化疗药物相比，新型靶向药物在控制中枢神经系统疾病方面似乎更有效，安全性更好。目前正在进行几项针对脑转移的各种靶向治疗的专门试验，以解决这些药物在中枢神经系统疾病治疗中的作用。本文综述了脑转移的基因组图谱研究的最新进展，以及乳腺癌、肺癌、结直肠癌、肾癌、卵巢癌和黑色素瘤脑转移靶向治疗的研究现状。
In the current era of molecularly targeted therapies and precision medicine, choice of cancer treatment has been increasingly tailored according to the molecular or genomic characterization of the cancer the individual has. Previously, the clinical observation of inadequate control of brain metastases was widely attributed to a lack of central nervous system (CNS) penetration of the anticancer drugs. However, more recent data have suggested that there are genetic explanations for such observations. Genomic analyses of brain metastases and matching primary tumor and other extracranial metastases have revealed that brain metastases can harbor potentially actionable driver mutations that are unique to them. Identification of genomic alterations specific to brain metastases and targeted therapies against these mutations represent an important research area to potentially improve survival outcomes for patients who develop brain metastases. Novel approaches in genomic testing such as that using cell-free circulating tumor DNA (ctDNA) in the cerebrospinal fluid (CSF) facilitate advancing our understanding of the genomics of brain metastases, which is critical for precision medicine. CSF-derived ctDNA sequencing may be particularly useful in patients who are unfit for surgical resection or have multiple brain metastases, which can harbor mutations that are distinct from their primary tumors. Compared to the traditional chemotherapeutics, novel targeted agents appear to be more effective in controlling the CNS disease with better safety profiles. Several brain metastases-dedicated trials of various targeted therapies are currently underway to address the role of these agents in the treatment of CNS disease. This review focuses on recent advances in genomic profiling of brain metastases and current knowledge of targeted therapies in the management of brain metastases from cancers of the breast, lung, colorectum, kidneys, and ovaries as well as melanoma.
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影响因子：
16.6
作者：
De Mattos-Arruda L;Mayor R;Ng CKY;Weigelt B;Martínez-Ricarte F;Torrejon D;Oliveira M;Arias A;Raventos C;Tang J;Guerini-Rocco E;Martínez-Sáez E;Lois S;Marín O;de la Cruz X;Piscuoglio S;Towers R;Vivancos A;Peg V;Ramon y Cajal S;Carles J;Rodon J;González-Cao M;Tabernero J;Felip E;Sahuquillo J;Berger MF;Cortes J;Reis-Filho JS;Seoane J
通讯作者：
Seoane J
DOI：
10.1016/s1470-2045(16)30053-5
发表时间：
2016-07
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Goldberg SB;Gettinger SN;Mahajan A;Chiang AC;Herbst RS;Sznol M;Tsiouris AJ;Cohen J;Vortmeyer A;Jilaveanu L;Yu J;Hegde U;Speaker S;Madura M;Ralabate A;Rivera A;Rowen E;Gerrish H;Yao X;Chiang V;Kluger HM
通讯作者：
Kluger HM
影响因子：
4.7
作者：
HARDY, JR;HARVEY, VJ
通讯作者：
HARVEY, VJ
影响因子：
51.1
作者：
Bachelot, Thomas;Romieu, Gilles;Labbe-Devilliers, Catherine
通讯作者：
Labbe-Devilliers, Catherine
影响因子：
5.8
作者：
Harding, James J.;Catalanotti, Federica;Chapman, Paul B.
通讯作者：
Chapman, Paul B.