Targeting the DNA damage response to overcome cancer drug resistance in glioblastoma

Research output: Contribution to journalReview articlepeer-review

Abstract

Glioblastoma multiforme (GBM) is a severe brain tumor whose ability to mutate and adapt to therapies is at the base for the extremely poor survival rate of patients. Despite multiple efforts to develop alternative forms of treatment, advances have been disappointing and GBM remains an arduous tumor to treat. One of the leading causes for its strong resistance is the innate upregulation of DNA repair mechanisms. Since standard therapy consists of a combinatory use of ionizing radiation and alkylating drugs, which both damage DNA, targeting the DNA damage response (DDR) is proving to be a beneficial strategy to sensitize tumor cells to treatment. In this review, we will discuss how recent progress in the availability of the DDR kinase inhibitors will be key for future therapy development. Further, we will examine the principal existing DDR inhibitors, with special focus on those currently in use for GBM clinical trials.

Original languageEnglish
Article number4910
Pages (from-to)1-19
Number of pages19
JournalInternational Journal of Molecular Sciences
Volume21
Issue number14
DOIs
Publication statusPublished - Jul 2 2020

Keywords

  • DDR inhibitors
  • DNA damage response
  • Glioblastoma

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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