Critical DNA damaging pathways in tumorigenesis

Jake A. Kloeber, Zhenkun Lou

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)164-184
Number of pages21
JournalSeminars in Cancer Biology
StatePublished - Oct 2022


  • DNA damage
  • Genome instability
  • Tumorigenesis

ASJC Scopus subject areas

  • Cancer Research


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