Blood-brain barrier, cytotoxic chemotherapies and glioblastoma

Abstract

Glioblastomas (GBM) are the most common and aggressive primary malignant brain tumors in adults. The blood brain barrier (BBB) is a major limitation reducing efficacy of anti-cancer drugs in the treatment of GBM patients. Areas covered: Virtually all GBM recur after the first-line treatment, at least partly, due to invasive tumor cells protected from chemotherapeutic agents by the intact BBB in the brain adjacent to tumor. The passage through the BBB, taken by antitumor drugs, is poorly and heterogeneously documented in the literature. In this review, we have focused our attention on: (i) the BBB, (ii) the passage of chemotherapeutic agents across the BBB and (iii) the strategies investigated to overcome this barrier. Expert commentary: A better preclinical knowledge of the crossing of the BBB by antitumor drugs will allow optimizing their clinical development, alone or combined with BBB bypassing strategies, towards an increased success rate of clinical trials.

Isoalantolactone inhibits IKKβ kinase activity to interrupt the NF‐κB/COX‐2‐mediated signaling cascade and induces apoptosis regulated by the mitochondrial translocation of cofilin in glioblastoma

“…The BBB is an important factor that limits the use of chemotherapeutic drugs in the treatment of GBM . The detection of the concentration of drugs injected into the bloodstream in the cerebrospinal fluid can demonstrate the penetration of the BBB .…”

How to Make Anticancer Drugs Cross the Blood–Brain Barrier to Treat Brain Metastases

“…Typically, albumin-bound Evans Blue dye injected intravenously accumulates in brain metastases, while it does not cross the BBB in the absence of metastases [35]. Morphologically, the blood-tumor barrier is anarchic, disorganized, sinuous, irregularly shaped, with large and leaky blood vessels [36]. Ultrathin-section electron microscopy has shown a redistribution of tight junctions on both sides (from the protoplasmic to the exoplasmic side) of the lipid bilayer [37].…”

Covalent nano delivery systems for selective imaging and treatment of brain tumors

“…Although the BBB has been observed to be altered at the tumor core (termed the “brain-tumor barrier”, or BTB) with somewhat disrupted selectivity (Fig. 4), it is intact adjacent to the BTB, allowing peripheral malignant cells to evade treatment [140]. Some possible mechanisms for BBB penetration include passive diffusion, active transport by transcytosis/endocytosis, or by inhibiting efflux pumps (Fig 5 [140]).…”

“…4), it is intact adjacent to the BTB, allowing peripheral malignant cells to evade treatment [140]. Some possible mechanisms for BBB penetration include passive diffusion, active transport by transcytosis/endocytosis, or by inhibiting efflux pumps (Fig 5 [140]). Furthermore, other physiological obstacles limit progress in brain cancer treatment, as will be described later in this review.…”

“…However, improvement in the outcome of GBM patients has remained dismal in the past 25 years. Today, the standard of care in brain tumor treatment consists of cytoreductive surgery, followed by chemotherapy [140, 144, 149, 150]. Along with radiation, Temozolomide (TMZ) continues to be the first line chemotherapy since its first approval for GBM treatment by FDA.…”