Critical DNA damaging pathways in tumorigenesis. (October 2022)

• Record Type: Journal Article
• Authors: Kloeber, Jake A.; Lou, Zhenkun
• Is Part Of: Seminars in cancer biology. Volume 85(2023)
• Page Start: 164
• Page End: 184
• Publication Date: 2022-10
• Subjects: DNA damage -- Tumorigenesis -- Genome instability; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2021.04.012
• Languages: English
• ISSNs: 1044-579X

Abstract

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.