Susceptibility of ATM-deficient pancreatic cancer cells to radiation

Michael Ayars1, James Eshleman1,2, Michael Goggins1,2,3

  • 1a Department of Pathology , The Johns Hopkins University School of Medicine , Baltimore , MD, USA.

Insights

Pancreatic cancer cells with inactivated Ataxia Telangiectasia Mutated (ATM) show increased sensitivity to radiation therapy. This finding suggests ATM status could predict radiotherapy response in pancreatic cancer patients.

Area of Science:

  • Oncology
  • Radiation Oncology
  • Molecular Biology

Background:

  • Ataxia Telangiectasia Mutated (ATM) is frequently inactivated in pancreatic ductal adenocarcinoma.
  • ATM status may serve as a predictive biomarker for treatment response in pancreatic cancer.

Purpose of the Study:

  • To investigate whether ATM deficiency sensitizes pancreatic cancer cells to fractionated radiation and common chemotherapeutics.
  • To explore the potential of ATM status as a predictor of radiotherapy response.

Main Methods:

  • ATM expression was reduced in three pancreatic cancer cell lines using ATM-targeting shRNA.
  • Isogenic cell lines were assessed for sensitivity to radiation and various chemotherapeutic agents.
  • DNA repair kinetics were analyzed post-irradiation using the comet assay.

Main Results:

  • ATM-deficient pancreatic cancer cells did not exhibit significantly altered sensitivity to tested chemotherapeutics.
  • ATM deficiency resulted in exquisite sensitization of pancreatic cancer cells to fractionated radiation.
  • DNA repair analysis indicated altered kinetics in irradiated ATM-deficient cells.

Conclusions:

  • ATM deficiency in pancreatic cancer cells sensitizes them to radiotherapy.
  • Pancreatic cancer ATM status may be a valuable biomarker for predicting radiotherapy efficacy.