Issues in Developing Drugs for Primary Brain Tumors: Barriers and Toxicities

Jeffrey Raizer*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Drug development in neuro-oncology remains a challenge for neoplasms of the central nervous system (CNS). Drugs can be administered peripherally (i.e., oral or intravenous) or locally (into the tumor or the adjacent neuropil). Each of these routes has advantages and disadvantages. Like the treatment for non-CNS cancers, peripheral side effects are encountered (i.e., diarrhea, myelosuppression, rash); however, there also may be neural-specific side effects for patients that may be acute or delayed (i.e., seizures, somnolence, hearing loss). The nervous system is also a privileged site protected by the blood-brain barrier, so many agents developed for peripheral administration will not penetrate into the CNS due to issues of size, charge, or lack of lipid solubility. In addition, the abnormal vasculature, increased interstitial pressure, and inherent mechanisms of tumor resistance (methyl-guanine-methyl transferase [MGMT], P-glycoprotein, etc.) within brain neoplasms reduce the efficacy of many agents designed for neuro-oncologic indications. Each of these issues alone, and all of them in aggregate, are reasons for the limited success of therapeutic agents directed against CNS tumors despite promising data acquired using cell lines and animal models.

Original languageEnglish (US)
Pages (from-to)152-157
Number of pages6
JournalToxicologic Pathology
Volume39
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • brain cancer
  • chemotherapy
  • drug development
  • glioma
  • nervous system
  • neuropathology
  • neurotoxicity
  • toxicity

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Toxicology
  • Cell Biology

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