The biology of brain metastases-translation to new therapies.
The biology of brain metastases-translation to new therapies.
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DOI：
10.1038/nrclinonc.2011.58
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发表时间：
2011-06
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脑转移是实体瘤患者治疗的严重障碍，并导致这些癌症的发病率和死亡率。据推测，脑转移频率增加的原因有多种，包括全身治疗和生存率的改善，以及无症状患者中转移灶的检测。缺乏概括临床环境的临床前模型以及将脑转移患者排除在大多数临床试验之外，导致进展缓慢。导致脑转移的分子因素正在被阐明，例如参与细胞粘附、外渗、代谢和细胞信号传导的基因。此外，独特的大脑微环境的作用也开始被探索。尽管血脑屏障在转移性肿瘤中的存在和功能仍然知之甚少，但血肿瘤屏障可能保护一些肿瘤细胞免受治疗，从而形成一个避难所。这篇综述讨论了关于脑转移生物学的已知信息、可用于研究该疾病的临床前模型以及正在对患者研究哪些新的治疗策略。
Brain metastases are a serious obstacle in the treatment of patients with solid tumors and contribute to the morbidity and mortality of these cancers. It is speculated that the frequency of brain metastasis is increasing for several reasons, including improved systemic therapy and survival, and detection of metastases in asymptomatic patients. The lack of preclinical models that recapitulate the clinical setting and the exclusion of patients with brain metastases from most clinical trials have slowed progress. Molecular factors contributing to brain metastases are being elucidated, such as genes involved in cell adhesion, extravasation, metabolism, and cellular signaling. Furthermore, the role of the unique brain microenvironment is beginning to be explored. Although the presence and function of the blood–brain barrier in metastatic tumors is still poorly understood, it is likely that some tumor cells are protected from therapeutics by the blood–tumor barrier, creating a sanctuary site. This Review discusses what is known about the biology of brain metastases, what preclinical models are available to study the disease, and which novel therapeutic strategies are being studied in patients.
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