Utilising DNA-PK inhibitor, M3814, as a radiation sensitizer

#3371

Introduction: A novel, clinical-stage DNA-PK inhibitor, M3814, potently and selectively blocks the NHEJ repair pathway for DNA double strand breaks (DSB).

Aim(s): Our study aims of radiosensitizing neuroendocrine (NET) cells with the DNA-PK inhibitor M3814, both in vitro and in preclinical NET models.

Materials and methods: 72-well clonogenic assays were evaluated for effective outcome of M3814 with radiation therapy (XRT) in vitro in BON and QGP-1 pancreatic NET cell lines. DSB-induced DNA repair was visualized with laser scanning microscopy. The activation of DNA-PKcs after M3814 treatment was confirmed by western blot. The efficacy of M3814 with XRT was evaluated in QGP-1 and BON human xenograft models. Tumor cells were injected into athymic nude mice, and treatment started when palpable tumors (∼200 mm3) were established. M3814 was given orally (100 mg/kg) 30 min prior to XRT.

Conference:

Presenting Author: Fatima A

Authors: Fatima A,

Keywords: DNA-PK inhibitor, M3814, DSB repair, NHEJ, XRT, BON,