Anti-tumoral activity of the G-quadruplex ligand pyridostatin against BRCA1/2-deficient tumours

ABSTRACT: Targeted therapies against BRCA1/2-mutated tumours introduce DNA lesions in tumour cells. Ligands that bind and stabilise G-quadruplexes (G4s) have recently emerged as a class of compounds that selectively eliminate cells and tumours lacking BRCA1/2. Pyridostatin is a small molecule that binds G4s and is specifically toxic to BRCA1/2-deficient cells in vitro. However, its in vivo potential has not yet been evaluated. Here we demonstrate that pyridostatin exhibits a high specific activity against BRCA1/2-deficient tumours, including PARPi resistant patient-derived xenograft tumours. Mechanistically, we demonstrate that pyridostatin disrupts replication leading to DNA double-stranded breaks that can be repaired in the absence of BRCA1/2 by canonical non-homologous end joining (C-NHEJ). Consi

SUBMITTER: Mr. Florian, J Groelly 

PROVIDER: S-SCDT-EMM-2021-14501 | biostudies-other |

REPOSITORIES: biostudies-other