Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong SAR, 999077, People's Republic of China.
Department of Radiology, Duke University Medical Center; 311 Research Drive, Box 3808, Durham, NC, 27710, USA.
Cancer Lett. 2020 Oct 1;489:174-181. doi: 10.1016/j.canlet.2020.06.012. Epub 2020 Jun 16.
Improvements in the diagnosis and treatment of systemic breast cancer have led to a prolongation in patient survival. Unfortunately, these advances are also associated with an increased incidence of brain metastases (BM), with the result that many patients succumb due to BM treatment failure. Intracranial delivery of many chemotherapeutic agents and other therapeutics is hindered by the presence of an impermeable blood-brain barrier (BBB) designed to protect the brain from harmful substances. The formation of BM compromises the integrity of the BBB, resulting in a highly heterogeneous blood-tumor barrier (BTB) with varying degrees of vascular permeability. Here, we discuss how blood vessels play an important role in the formation of brain micrometastases as well as in the transformation from poorly permeable BM to highly permeable BM. We then review the role of BTB vascular permeability in the diagnostics and the choice of treatment regimens for breast cancer brain metastases (BCBM) and discuss whether the vasculature of primary breast cancers can serve as a biomarker for BM. Specifically, we examine the association between the vascular permeability of BCBM and their accumulation of large molecules such as antibodies, which remains largely unexplored.
系统乳腺癌的诊断和治疗的改进导致了患者生存时间的延长。不幸的是，这些进展也与脑转移（BM）的发生率增加有关，导致许多患者因 BM 治疗失败而死亡。许多化疗药物和其他治疗药物的颅内递送受到血脑屏障（BBB）的阻碍，该屏障旨在保护大脑免受有害物质的侵害。BM 的形成破坏了 BBB 的完整性，导致具有不同程度血管通透性的高度异质血肿瘤屏障（BTB）。在这里，我们讨论了血管在脑微转移的形成以及从通透性差的 BM 向通透性高的 BM 的转变中所起的重要作用。然后，我们回顾了 BTB 血管通透性在乳腺癌脑转移（BCBM）的诊断和治疗方案选择中的作用，并讨论了原发性乳腺癌的血管是否可以作为 BM 的标志物。具体来说，我们研究了 BCBM 的血管通透性与其对大分子（如抗体）的积累之间的关系，这在很大程度上仍未得到探索。
