脑转移瘤有效药物治疗的障碍：精准医学实施中的多因素问题。
Barriers to Effective Drug Treatment for Brain Metastases: A Multifactorial Problem in the Delivery of Precision Medicine.
机构信息
University of Minnesota, Minneapolis, Minnesota, USA.
Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
出版信息
Pharm Res. 2018 Jul 12;35(9):177. doi: 10.1007/s11095-018-2455-9.
Abstract
The treatment of metastatic lesions in the brain represents a serious unmet medical need in the field of neuro-oncology. Even though many effective compounds have demonstrated success in treating peripheral (non-CNS) tumors with targeted agents, one aspect of this lack of success in the brain may be related to poor delivery of otherwise effective compounds. Many factors can influence the brain delivery of these agents, but one key barrier is a heterogeneously "leaky" BBB that expresses efflux transporters that limit the BBB permeability for many targeted agents. Future success in therapeutics for brain metastases must take into account the adequate delivery of "active, free drug" to the target, and may include combinations of targeted drugs that are appropriate to address each individual patient's tumor type. This review discusses some issues that are pertinent to precision medicine for brain metastases, using specific examples of tumor types that have a high incidence of brain metastases.
摘要
脑转移瘤的治疗是神经肿瘤学领域尚未满足的重大医学需求。尽管许多有效的化合物已通过靶向药物在治疗外周（非 CNS）肿瘤方面取得成功，但这些药物在脑部治疗效果不佳的一个原因可能与其他有效的化合物在脑部的递送效率较差有关。许多因素都会影响这些药物在脑部的递送，但一个关键的障碍是 BBB 存在异质性渗漏，表达外排转运体，使许多靶向药物的 BBB 通透性受限。未来脑转移瘤治疗的成功必须考虑将“活性游离药物”充分递送至靶标，这可能包括针对每个患者肿瘤类型的靶向药物联合应用。本文通过特定的高脑转移发生率肿瘤类型的实例，讨论了与脑转移瘤精准医学相关的一些问题。
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