Blood-brain barrier, cytotoxic chemotherapies and glioblastoma

ABSTRACT

Introduction: 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.

KEYWORDS:

• Glioblastoma
• blood-brain barrier
• cytotoxic chemotherapy
• pharmacokinetics
• delivery

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Corrigendum

Declaration of interest

The research leading to these results has received funding from the program ‘Investissements d’avenir’ ANR-10-IAIHU-06. Institut Universitaire de Cancérologie (IUC). A Dréan is funded by Carthera SAS. This work is part of GlioTex (i.e. GBM and Experimental Therapeutics) project funded by La Fondation ARC pour la Recherche sur le Cancer. A Idbaih discloses funds from Carthera SAS, Gekco, Bristol Myers Squibb, Hoffmann-La Roche. M Canney and A Carpentier disclose funds from Carthera SAS. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.