Targeting DNA Damage Response-Mediated Resistance in Non-Small Cell Lung Cancer: From Mechanistic Insights to Drug Development
Non-small cell lung cancer (NSCLC) remains a major contributor to cancer-related deaths worldwide, with therapeutic resistance presenting a critical clinical hurdle. The DNA damage response (DDR) constitutes a sophisticated cellular framework that detects, signals, and repairs genetic lesions to pre...
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| Format: | Article |
| Language: | English |
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MDPI AG
2025-06-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/32/7/367 |
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| author | Xue Gong Yongzhao Zhou Yi Deng |
| author_facet | Xue Gong Yongzhao Zhou Yi Deng |
| author_sort | Xue Gong |
| collection | DOAJ |
| description | Non-small cell lung cancer (NSCLC) remains a major contributor to cancer-related deaths worldwide, with therapeutic resistance presenting a critical clinical hurdle. The DNA damage response (DDR) constitutes a sophisticated cellular framework that detects, signals, and repairs genetic lesions to preserve genomic stability. While the DDR plays a crucial role in determining the efficacy of radiotherapy and chemotherapy, current research primarily focuses on direct DDR inhibitors, often overlooking the broader regulatory networks that modulate DDR activity. This review aims to comprehensively analyze the upstream and downstream pathways governing DDR in NSCLC, highlighting key molecular regulators, signaling interactions, and potential feedback mechanisms contributing to therapy resistance. By identifying novel regulatory targets and clinically relevant biomarkers, we propose innovative therapeutic strategies to enhance treatment efficacy. Our approach seeks to bridge the gap between DDR dysregulation and precision oncology, offering new perspectives on overcoming resistance and improving patient outcomes in NSCLC. |
| format | Article |
| id | doaj-art-85c8a25d0f7a42dbb4b0105838f80a79 |
| institution | DOAJ |
| issn | 1198-0052 1718-7729 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj-art-85c8a25d0f7a42dbb4b0105838f80a792025-08-20T03:07:57ZengMDPI AGCurrent Oncology1198-00521718-77292025-06-0132736710.3390/curroncol32070367Targeting DNA Damage Response-Mediated Resistance in Non-Small Cell Lung Cancer: From Mechanistic Insights to Drug DevelopmentXue Gong0Yongzhao Zhou1Yi Deng2Integrated Care Management Center, Institute of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu 610041, ChinaIntegrated Care Management Center, Institute of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu 610041, ChinaIntegrated Care Management Center, Institute of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu 610041, ChinaNon-small cell lung cancer (NSCLC) remains a major contributor to cancer-related deaths worldwide, with therapeutic resistance presenting a critical clinical hurdle. The DNA damage response (DDR) constitutes a sophisticated cellular framework that detects, signals, and repairs genetic lesions to preserve genomic stability. While the DDR plays a crucial role in determining the efficacy of radiotherapy and chemotherapy, current research primarily focuses on direct DDR inhibitors, often overlooking the broader regulatory networks that modulate DDR activity. This review aims to comprehensively analyze the upstream and downstream pathways governing DDR in NSCLC, highlighting key molecular regulators, signaling interactions, and potential feedback mechanisms contributing to therapy resistance. By identifying novel regulatory targets and clinically relevant biomarkers, we propose innovative therapeutic strategies to enhance treatment efficacy. Our approach seeks to bridge the gap between DDR dysregulation and precision oncology, offering new perspectives on overcoming resistance and improving patient outcomes in NSCLC.https://www.mdpi.com/1718-7729/32/7/367non-small cell lung cancerDNA damage responsedrug resistanceradiotherapychemotherapytargeted therapy |
| spellingShingle | Xue Gong Yongzhao Zhou Yi Deng Targeting DNA Damage Response-Mediated Resistance in Non-Small Cell Lung Cancer: From Mechanistic Insights to Drug Development Current Oncology non-small cell lung cancer DNA damage response drug resistance radiotherapy chemotherapy targeted therapy |
| title | Targeting DNA Damage Response-Mediated Resistance in Non-Small Cell Lung Cancer: From Mechanistic Insights to Drug Development |
| title_full | Targeting DNA Damage Response-Mediated Resistance in Non-Small Cell Lung Cancer: From Mechanistic Insights to Drug Development |
| title_fullStr | Targeting DNA Damage Response-Mediated Resistance in Non-Small Cell Lung Cancer: From Mechanistic Insights to Drug Development |
| title_full_unstemmed | Targeting DNA Damage Response-Mediated Resistance in Non-Small Cell Lung Cancer: From Mechanistic Insights to Drug Development |
| title_short | Targeting DNA Damage Response-Mediated Resistance in Non-Small Cell Lung Cancer: From Mechanistic Insights to Drug Development |
| title_sort | targeting dna damage response mediated resistance in non small cell lung cancer from mechanistic insights to drug development |
| topic | non-small cell lung cancer DNA damage response drug resistance radiotherapy chemotherapy targeted therapy |
| url | https://www.mdpi.com/1718-7729/32/7/367 |
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