Tumor-treating fields elicit a conditional vulnerability to ionizing radiation via the downregulation of BRCA1 signaling and reduced DNA double-strand break repair capacity in non-small cell lung cancer cell lines

Authors: Karanam NK, Srinivasan K, Ding L, Sishc B, Saha D, Story MD

Year: 2017 Mar 30

Category: Oncology, Genetics

Journal: Cell Death Dis

DOI: 10.1038/cddis.2017.136

URL: https://www.ncbi.nlm.nih.gov/pubmed/28358361

Abstract

Overview

The use of tumor-treating fields (TTFields) has revolutionized the treatment of glioblastoma and is now being studied in non-small cell lung cancer (NSCLC). TTFields apply low-intensity, intermediate frequency, alternating electric fields using non-invasive arrays targeted at tumor areas.

Findings

TTFields treatment in NSCLC cell lines shows:

  • Varied cell proliferation and killing rates, unrelated to p53 status.
  • Increase in G2/M cell population and a decrease in S-phase cells, leading to apoptosis.
  • Significant downregulation of BRCA1 mediated DNA-damage response and increased DNA double-strand breaks.
  • Exposure post-ionizing radiation enhances chromatid aberrations and reduces DNA repair capability.

Conclusion

TTFields induce a state of 'BRCAness' that increases susceptibility to ionizing radiation, suggesting their potential as a complementary therapy with existing DNA-damaging treatments.

TTFields NSCLC BRCA1 DNA repair cell cycle apoptosis radiation therapy
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