Barriers to Effective Drug Treatment for Brain Metastases: A Multifactorial Problem in the Delivery of Precision Medicine

Minjee Kim, Sani H. Kizilbash, Janice K. Laramy, Gautham Gampa, Karen E. Parrish, Jann N. Sarkaria, William F. Elmquist

Research output: Contribution to journalReview article

8 Scopus citations

Abstract

The treatment of metastatic lesions in the brain represents a serious unmet medical need in the field of neuro-oncology. Even though many effective compounds have demonstrated success in treating peripheral (non-CNS) tumors with targeted agents, one aspect of this lack of success in the brain may be related to poor delivery of otherwise effective compounds. Many factors can influence the brain delivery of these agents, but one key barrier is a heterogeneously “leaky” BBB that expresses efflux transporters that limit the BBB permeability for many targeted agents. Future success in therapeutics for brain metastases must take into account the adequate delivery of “active, free drug” to the target, and may include combinations of targeted drugs that are appropriate to address each individual patient’s tumor type. This review discusses some issues that are pertinent to precision medicine for brain metastases, using specific examples of tumor types that have a high incidence of brain metastases.

Original languageEnglish (US)
Article number177
JournalPharmaceutical research
Volume35
Issue number9
DOIs
StatePublished - Sep 1 2018

Keywords

  • blood-brain barrier
  • brain metastases
  • drug delivery
  • efflux transporters
  • metastasize
  • molecularly-targeted anti-cancer agents

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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