Critical DNA damaging pathways in tumorigenesis

Semin Cancer Biol. 2022 Oct:85:164-184. doi: 10.1016/j.semcancer.2021.04.012. Epub 2021 Apr 24.

Abstract

The acquisition of DNA damage is an early driving event in tumorigenesis. Premalignant lesions show activated DNA damage responses and inactivation of DNA damage checkpoints promotes malignant transformation. However, DNA damage is also a targetable vulnerability in cancer cells. This requires a detailed understanding of the cellular and molecular mechanisms governing DNA integrity. Here, we review current work on DNA damage in tumorigenesis. We discuss DNA double strand break repair, how repair pathways contribute to tumorigenesis, and how double strand breaks are linked to the tumor microenvironment. Next, we discuss the role of oncogenes in promoting DNA damage through replication stress. Finally, we discuss our current understanding on DNA damage in micronuclei and discuss therapies targeting these DNA damage pathways.

Keywords: DNA damage; Genome instability; Tumorigenesis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Transformation, Neoplastic / metabolism
  • DNA
  • DNA Breaks, Double-Stranded
  • DNA Damage*
  • DNA Repair* / genetics
  • Genomic Instability
  • Humans
  • Tumor Microenvironment

Substances

  • DNA