WINDOW consortium: A path towards increased therapy efficacy against glioblastoma

Research output: Contribution to journalArticle

Authors

  • Kulsoom U. Abdul
  • Megan Houweling
  • Fredrik Svensson
  • Ravi S. Narayan
  • Fleur M. G. Cornelissen
  • Asli Küçükosmanoglu
  • Emmanouil Metzakopian
  • David Bailey
  • Tom Wurdinger
  • Bart A. Westerman

Colleges, School and Institutes

External organisations

  • UK Dementia Research Institute
  • IOTA Pharmaceuticals Ltd.
  • Academic Medical Center, University of Amsterdam

Abstract

Glioblastoma is the most common and malignant form of brain cancer, for which the standard treatment is maximal surgical resection, radiotherapy and chemotherapy. Despite these interventions, mean overall survival remains less than 15 months, during which extensive tumor infiltration throughout the brain occurs. The resulting metastasized cells in the brain are characterized by chemotherapy resistance and extensive intratumoral heterogeneity. An orthogonal approach attacking both intracellular resistance mechanisms as well as intercellular heterogeneity is necessary to halt tumor progression. For this reason, we established the WINDOW Consortium (Window for Improvement for Newly Diagnosed patients by Overcoming disease Worsening), in which we are establishing a strategy for rational selection and development of effective therapies against glioblastoma. Here, we overview the many challenges posed in treating glioblastoma, including selection of drug combinations that prevent therapy resistance, the need for drugs that have improved blood brain barrier penetration and strategies to counter heterogeneous cell populations within patients. Together, this forms the backbone of our strategy to attack glioblastoma.

Details

Original languageEnglish
Pages (from-to)17-24
Number of pages8
JournalDrug Resistance Updates
Volume40
Publication statusPublished - 30 Oct 2018

Keywords

  • glioblastoma, therapy resistance, combination therapy, small molecule drugs, blood brain barrier, toxicity