Resistance to minor groove binders

Benedetta Colmegna, Sarah Uboldi, Eugenio Erba, Maurizio D'Incalci

Research output: Contribution to journalArticlepeer-review

Abstract

In this paper multiple resistance mechanisms to minor groove binders (MGBs) are overviewed. MGBs with antitumor properties are natural products or their derivatives and, as expected, they are all substrates of P-glycoprotein (P-gp). However, a moderate expression of P-gp does not appear to reduce the sensitivity to trabectedin, the only MGB so far approved for clinical use. Resistance to this drug is often related to transcriptional mechanisms and to DNA repair pathways, particularly defects in transcription-coupled nucleotide excision repair (TC-NER). Therefore tumors resistant to trabectedin may become hypersensitive to UV rays and other DNA damaging agents acting in the major groove, such as Platinum (Pt) complexes. If this is confirmed in clinic, that will provide the rationale to combine trabectedin sequentially with Pt derivates.

Original languageEnglish
Pages (from-to)73-79
Number of pages7
JournalDrug Discovery Today: Technologies
Volume11
Issue number1
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Drug Discovery
  • Biotechnology
  • Molecular Medicine
  • Medicine(all)

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