Abstract
Brain tumors are characterized by very high mortality and, despite the continuous research on new pharmacological interventions, little therapeutic progress has been made. One of the main obstacles to improve current treatments is represented by the impermeability of the blood vessels residing within nervous tissue as well as of the new vascular net generating from the tumor, commonly referred to as blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), respectively. In this review, we focused on established and emerging strategies to overcome the blood-brain barrier to increase drug delivery for brain cancer. To date, there are three broad strategies being investigated to cross the brain vascular wall and they are conceived to breach, bypass, and negotiate the access to the nervous tissue. In this paper, we summarized these approaches highlighting their working mechanism and their potential impact on the quality of life of the patients as well as their current status of development.
Highlights
Tumors of the central nervous system (CNS) account for about 3% [1,2] of the worldwide diagnosed neoplastic diseases and represent one of the most frequent causes of solid tumor-related deaths in childhood [3]
In the case of brain tumors, the development of more effective treatments is hampered by the specialized barrier function that characterizes the blood vessels residing in the central nervous system and usually referred to as the blood-brain barrier (BBB)
The barrier function of the CNS endothelium is determined by other cell phenotypes and biological structures including astrocytes, pericytes, microglia cells, neurons, and basement membranes which when taken with the endothelial cells, constitute what is commonly known as the neurovascular unit (Figure 1)
Summary
Tumors of the central nervous system (CNS) account for about 3% [1,2] of the worldwide diagnosed neoplastic diseases and represent one of the most frequent causes of solid tumor-related deaths in childhood [3]. The Stupp protocol is the gold-standard treatment for GBM [8], and it consists of surgical resection, postoperative radiotherapy, and temozolomide (TMZ), often used in association with adjuvant therapies including carmustine and PCV (procarbazine, lomustine, and vincristine). Despite their significant cytostatic properties in vitro, many Food and Drug Administration approved chemotherapeutics have shown limited curative benefits in the clinic. In the case of brain tumors, the development of more effective treatments is hampered by the specialized barrier function that characterizes the blood vessels residing in the central nervous system and usually referred to as the blood-brain barrier (BBB). We describe new clinical and experimental approaches that aim to disrupt, bypass and negotiate these vascular barriers to favor the accumulation of therapeutics in brain cancer tissue
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