The DNA Damage Response: Implications for Tumor Responses to Radiation and Chemotherapy
Abstract
Cellular responses to DNA damage are important determinants of both cancer development and cancer outcome following radiation therapy and chemotherapy. Identification of molecular pathways governing DNA damage signaling and DNA repair in response to different types of DNA lesions allows for a better understanding of the effects of radiation and chemotherapy on normal and tumor cells. Although dysregulation of the DNA damage response (DDR) is associated with predisposition to cancer development, it can also result in hypersensitivity or resistance of tumors to therapy and can be exploited for improvement of cancer treatment. We highlight the DDR pathways that are activated after treatment with radiation and different classes of chemotherapeutic drugs and describe mechanisms determining tumor sensitivity and resistance to these agents. Further, we discuss approaches to enhance tumor sensitivity to radiation and chemotherapy by modulating the DDR with a goal of enhancing the effectiveness of cancer therapies.
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Deregulation of posttranslational modifications of proteins inside tumor cells is a main factor related to radioresistance.
“A main factor related to radioresistance is the deregulation of the posttranslational modifications of proteins inside tumor cells that are responsible for the activation of DNA repair pathways and the inhibition of apoptosis4.”
From An HDAC4-specific PROTAC degrader achieves radiation sensitization by enhancing ferroptosis in lung cancer (2026) · cites this paper as [4]
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- Authors
- Goldstein, M., & Kastan, M. B.
- Affiliations
- Duke University (US)
- Venue
- Annual Review of Medicine
- Publisher
- Annual Reviews
- Published
- 2015-01-14
- Volume
- 66
- Issue
- 1
- Pages
- 129-143
- ISSN
- 0066-4219 (ISSN-L)
- 1545-326X
- OpenAlex
- W2151252396
- Cited by
- 590
- References
- 8
- Citations by year
- 2026: 40 · 2025: 62 · 2024: 67 · 2023: 72 · 2022: 75 · 2021: 83 · 2020: 54 · 2019: 44 · 2018: 27 · 2017: 27 · 2016: 32 · 2015: 5
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- DNA damage response, radiotherapy, chemotherapy, DNA repair, DNA damage signaling, tumor sensitivity, tumor resistance, chemoresistance, radiosensitivity, cancer susceptibility, DNA lesions
- MeSH terms
- Antineoplastic Agents, DNA Damage, DNA Repair, Humans, Neoplasms, Radiotherapy, DNA Methylation
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