Blood-brain barrier (BBB) and blood-tumor barrier (BTB)

The composition of the BBB is well understood. It is composed of continuous endothelial cells with distinct tight junctions and efflux transporters to remove metabolic waste, a basement membrane, multiple subpopulations of pericytes, and astrocyte endfeet. The BBB plays a critical role in controlling the exchange of molecules between the neuroparenchyma, vasculature, and cerebrospinal fluid spaces 1. Paracellular routes, composed of endothelial cell tight junctions, and transcellular routes, composed of endocytic caveolae, prevent passage of damaging agents or compounds from entering the neuroparenchyma.1

Brain metastases result in the disruption of BBB and the formation of BTB. Brain metastases have minimal chemotherapeutic uptake and some have been identified as heterogeneously permeable.2 While the BTB disruption does elicit disruption, the BTB still prevents uptake and absorption of pharmaceutical agents in to the neuroparenchyma 3. A number of drug delivery mechanisms have been employed in primary and metastatic brain tumors, including nanoparticle drug delivery, chemical mediated BTB permeability, efflux pump inhibitors, and intraventricular delivery.3 An understanding of the pathology of the disease is critical to developing targeting molecular mechanisms to treat the disease.

References

  1. Abbott NJ, Patabendige AAK, Dolman DEM, Yusof SR, Begley DJ: Structure and function of the blood–brain barrier. Neurobiol Dis 2010, 37:13–25.
  2. Lyle LT, Lockman PR, Adkins CE, Mohammad AS, Sechrest E, Hua E, Palmieri D, Liewehr DJ, Steinberg SM, Kloc W, Izycka-Swieszewska E, Duchnowska R, Nayyar N, Brastianos PK, Steeg PS, Gril B: Alterations in Pericyte Subpopulations Are Associated with Elevated Blood–Tumor Barrier Permeability in Experimental Brain Metastasis of Breast Cancer. Clin Cancer Res 2016, 22:5287.
  3. Hendricks BK, Cohen-Gadol AA, Miller JC: Novel delivery methods bypassing the blood-brain and blood-tumor barriers. Neurosurg Focus 2015, 38:E10.

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