Molecular Profiles of Brain Metastases: A Focus on Heterogeneity.
Molecular Profiles of Brain Metastases: A Focus on Heterogeneity.
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DOI：
10.3390/cancers13112645
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发表时间：
2021-05-28
期刊：
影响因子：
5.2
通讯作者：
Jassem J
中科院分区：
文献类型：
--
作者：
Ali S;Górska Z;Duchnowska R;Jassem J
精确的癌症医学取决于肿瘤样本的特征，通常是通过单个肿瘤活检来进行最佳治疗。然而，原发性肿瘤及其转移瘤通常是异质性的。转移性病变可能具有与其母体肿瘤完全不同的遗传组成，并且单一肿瘤取样可能在选择最有效的治疗中无效。脑转移瘤由于其低可用性和特定的微环境，对精准医疗提出了特殊的挑战。在这篇综述中，我们强调了脑转移瘤的遗传景观，特别关注其异质性。为了说明这个问题，我们提出了肺癌，乳腺癌和黑色素瘤脑转移的表型改变。这篇文章可能有助于临床医生更好地了解脑转移瘤的变化及其异质性的相关性。脑转移瘤是一种常见的和毁灭性的临床实体。脑转移瘤的瘤内异质性对精准医学提出了关键挑战。然而，下一代测序的进展，对驱动突变的病理生理学的新见解以及新型肿瘤模型的创建使我们能够更好地了解脑转移瘤的遗传景观，其时间演变及其对各种治疗的反应。大量的基因组研究已经确定了肿瘤的异质性克隆景观，同时为精准医学引入了潜在的靶点。作为一个例子，我们提出了脑转移的表型改变起源于三种恶性肿瘤与最高的脑转移频率：肺癌，乳腺癌，黑色素瘤。我们讨论了精准医学的障碍，肿瘤异质性，血液生物标志物在跟踪克隆进化中的意义，原发性和转移性肿瘤之间的系统发育关系，血脑屏障异质性以及正在进行的研究的局限性。
Precision cancer medicine depends on the characterization of tumor samples, usually by a single-tumor biopsy, to administer an optimal therapeutic. However, primary tumors and their metastases are often heterogeneous. A metastatic lesion may harbor a completely different genetic makeup to that of its parent tumor, and a single tumor sampling may be ineffective in selecting the most efficient therapy. Brain metastases, due to their low availability and specific microenvironment, pose a particular challenge for precision medicine. In this review, we highlight the genetic landscape of brain metastases, with a particular focus on their heterogeneity. To illustrate this problem, we present phenotypic alterations in brain metastases originating from lung cancer, breast cancer, and melanoma. This article may help clinicians better understand alterations in brain metastases and the relevance of their heterogeneity. Brain metastasis is a common and devastating clinical entity. Intratumor heterogeneity in brain metastases poses a crucial challenge to precision medicine. However, advances in next-generation sequencing, new insight into the pathophysiology of driver mutations, and the creation of novel tumor models have allowed us to gain better insight into the genetic landscapes of brain metastases, their temporal evolution, and their response to various treatments. A plethora of genomic studies have identified the heterogeneous clonal landscape of tumors and, at the same time, introduced potential targets for precision medicine. As an example, we present phenotypic alterations in brain metastases originating from three malignancies with the highest brain metastasis frequency: lung cancer, breast cancer, and melanoma. We discuss the barriers to precision medicine, tumor heterogeneity, the significance of blood-based biomarkers in tracking clonal evolution, the phylogenetic relationship between primary and metastatic tumors, blood–brain barrier heterogeneity, and limitations to ongoing research.
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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
影响因子：
6.2
作者：
Gong, Yun;Han, Eric Yulong;Sneige, Nour
通讯作者：
Sneige, Nour
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4
作者：
Fitzgerald, Daniel P.;Palmieri, Diane;Hua, Emily;Hargrave, Elizabeth;Herring, Jeanne M.;Qian, Yongzhen;Vega-Valle, Eleazar;Weil, Robert J.;Stark, Andreas M.;Vortmeyer, Alexander O.;Steeg, Patricia S.
通讯作者：
Steeg, Patricia S.
影响因子：
--
作者：
De Mattos-Arruda L;Ng CKY;Piscuoglio S;Gonzalez-Cao M;Lim RS;De Filippo MR;Fusco N;Schultheis AM;Ortiz C;Viteri S;Arias A;Macedo GS;Oliveira M;Gomez P;Teixidó C;Nuciforo P;Peg V;Saura C;Ramon Y Cajal S;Casas FT;Weigelt B;Cortes J;Seoane J;Reis-Filho JS
通讯作者：
Reis-Filho JS