Targeting glioblastoma-derived pericytes improves chemotherapeutic outcome

Angiogenesis. 2018 Nov;21(4):667-675. doi: 10.1007/s10456-018-9621-x. Epub 2018 May 14.

Abstract

Glioblastoma is the most common malignant brain cancer in adults, with poor prognosis. The blood-brain barrier limits the arrival of several promising anti-glioblastoma drugs, and restricts the design of efficient therapies. Recently, by using state-of-the-art technologies, including thymidine kinase targeting system in combination with glioblastoma xenograft mouse models, it was revealed that targeting glioblastoma-derived pericytes improves chemotherapy efficiency. Strikingly, ibrutinib treatment enhances chemotherapeutic effectiveness, by targeting pericytes, improving blood-brain barrier permeability, and prolonging survival. This study identifies glioblastoma-derived pericyte as a novel target in the brain tumor microenvironment during carcinogenesis. Here, we summarize and evaluate recent advances in the understanding of pericyte's role in the glioblastoma microenvironment.

Keywords: Blood–brain barrier; Chemotherapy; Glioblastoma; Pericytes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenine / analogs & derivatives
  • Animals
  • Blood-Brain Barrier / metabolism*
  • Blood-Brain Barrier / pathology
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Drug Delivery Systems / methods*
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Mice
  • Pericytes / metabolism*
  • Pericytes / pathology
  • Piperidines
  • Pyrazoles / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Tumor Microenvironment / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Piperidines
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Adenine