Heterogeneity and vascular permeability of breast cancer brain metastases

Abstract

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.

Multispecific Platinum(IV) Complex Deters Breast Cancer via Interposing Inflammation and Immunosuppression as an Inhibitor of COX‐2 and PD‐L1

“…BCs are traditionally considered immunologically cold and BC patients are almost never enrolled in such clinical trials. [57] Lack of effective therapeutic target is the toughest problem in the treatment of TNBC. [58] This study provides af easible option to solve the problem by combining chemotherapy and immunotherapy in ap latinum complex.…”

“…Conversely, DNP suppresses the immune escape and stimulates anticancer immune response, presenting an anticancer activity far more powerful than the parent compounds cisplatin and naproxen. BCs are traditionally considered immunologically cold and BC patients are almost never enrolled in such clinical trials [57] . Lack of effective therapeutic target is the toughest problem in the treatment of TNBC [58] .…”

Blocking c-MET/ERBB1 Axis Prevents Brain Metastasis in ERBB2+ Breast Cancer

“…The BBB is selectively permeable under normal physiological conditions. However, the pathological cues, including brain metastasis, render the loss of BBB integrity, which transforms the intact BBB into the blood–tumor barrier (BTB) and alters the permeability for therapeutic agents [ 32 , 33 , 34 ]. As the SKBrM3 cell line expresses high c-MET and ERBB1 receptors, and the combination treatment of NER and CBZ predominantly downregulated the pERK pathway in this cell line, we examined the effect of treatment on the migration of SKBrM3 cell line in vitro that mimics the human BBB to some extent ( Figure 2 E).…”

Treating Metastatic Brain Cancers With Stem Cells

“…Through interleukin 1-Beta-mediated NF-kB signaling, these metastatic cells can drive the transformation of healthy astrocytes into tumor associated astrocytes (TAAs) that foster tumor expansion ( Xing et al, 2016 ). Once metastatic cancer cells overwhelm the BBB, the structure develops into a highly variable blood-tumor barrier (BTB), which exhibits various levels of permeability ( Babak et al, 2020 ).…”