Critical DNA damaging pathways in tumorigenesis

Jake A. Kloeber; Zhenkun Lou

doi:10.1016/j.semcancer.2021.04.012

Critical DNA damaging pathways in tumorigenesis

Jake A. Kloeber, Zhenkun Lou

Oncology

Research output: Contribution to journal › Review article › peer-review

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.

Original language	English (US)
Pages (from-to)	164-184
Number of pages	21
Journal	Seminars in Cancer Biology
Volume	85
DOIs	https://doi.org/10.1016/j.semcancer.2021.04.012
State	Published - Oct 2022

Keywords

DNA damage
Genome instability
Tumorigenesis

ASJC Scopus subject areas

Cancer Research

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10.1016/j.semcancer.2021.04.012

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title = "Critical DNA damaging pathways in tumorigenesis",

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",

author = "Kloeber, {Jake A.} and Zhenkun Lou",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",

year = "2022",

month = oct,

doi = "10.1016/j.semcancer.2021.04.012",

language = "English (US)",

volume = "85",

pages = "164--184",

journal = "Seminars in Cancer Biology",

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T1 - Critical DNA damaging pathways in tumorigenesis

AU - Kloeber, Jake A.

AU - Lou, Zhenkun

PY - 2022/10

Y1 - 2022/10

N2 - 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.

AB - 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.

KW - DNA damage

KW - Genome instability

KW - Tumorigenesis

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U2 - 10.1016/j.semcancer.2021.04.012

DO - 10.1016/j.semcancer.2021.04.012

M3 - Review article

C2 - 33905873

AN - SCOPUS:85105784072

SN - 1044-579X

VL - 85

SP - 164

EP - 184

JO - Seminars in Cancer Biology

JF - Seminars in Cancer Biology

ER -

Critical DNA damaging pathways in tumorigenesis

Abstract

Keywords

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