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Clinical translation for targeting DNA damage repair in non-small cell lung cancer: a review

Despite significant advancements in screening, diagnosis, and treatment of non-small cell lung cancer (NSCLC), it remains the primary cause of cancer-related deaths globally. DNA damage is caused by the exposure to exogenous and endogenous factors and the correct functioning of DNA damage repair (DD...

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Main Authors: Mao, Xinru, Lee, Nung Kion, Saad, Shaban Eljali, Isabel, Fong Lim
Format: Article
Language:English
Published: AME Publishing Company 2024
Subjects:
Q Science (General)
QR Microbiology
Online Access:http://ir.unimas.my/id/eprint/44449/2/Clinical.pdf
http://ir.unimas.my/id/eprint/44449/
https://tlcr.amegroups.org/article/view/83672/html
https://dx.doi.org/10.21037/tlcr-23-742
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spelling my.unimas.ir.444492024-03-11T08:05:01Z http://ir.unimas.my/id/eprint/44449/ Clinical translation for targeting DNA damage repair in non-small cell lung cancer: a review Mao, Xinru Lee, Nung Kion Saad, Shaban Eljali Isabel, Fong Lim Q Science (General) QR Microbiology Despite significant advancements in screening, diagnosis, and treatment of non-small cell lung cancer (NSCLC), it remains the primary cause of cancer-related deaths globally. DNA damage is caused by the exposure to exogenous and endogenous factors and the correct functioning of DNA damage repair (DDR) is essential to maintain of normal cell circulation. The presence of genomic instability, which results from defective DDR, is a critical characteristic of cancer. The changes promote the accumulation of mutations, which are implicated in cancer cells, but these may be exploited for anti-cancer therapies. NSCLC has a distinct genomic profile compared to other tumors, making precision medicine essential for targeting actionable gene mutations. Although various treatment options for NSCLC exist including chemotherapy, targeted therapy, and immunotherapy, drug resistance inevitably arises. The identification of deleterious DDR mutations in 49.6% of NSCLC patients has led to the development of novel target therapies that have the potential to improve patient outcomes. Synthetic lethal treatment using poly (ADP-ribose) polymerase (PARP) inhibitors is a breakthrough in biomarker-driven therapy. Additionally, promising new compounds targeting DDR, such as ATR, CHK1, CHK2, DNA-PK, and WEE1, had demonstrated great potential for tumor selectivity. In this review, we provide an overview of DDR pathways and discuss the clinical translation of DDR inhibitors in NSCLC, including their application as single agents or in combination with chemotherapy, radiotherapy, and immunotherapy. AME Publishing Company 2024 Article PeerReviewed text en http://ir.unimas.my/id/eprint/44449/2/Clinical.pdf Mao, Xinru and Lee, Nung Kion and Saad, Shaban Eljali and Isabel, Fong Lim (2024) Clinical translation for targeting DNA damage repair in non-small cell lung cancer: a review. Translational Lung Cancer Research, 13 (2). pp. 375-397. ISSN 2226-4477) https://tlcr.amegroups.org/article/view/83672/html https://dx.doi.org/10.21037/tlcr-23-742
institution Universiti Malaysia Sarawak
building Centre for Academic Information Services (CAIS)
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaysia Sarawak
content_source UNIMAS Institutional Repository
url_provider http://ir.unimas.my/
language English
topic Q Science (General)
QR Microbiology
spellingShingle Q Science (General)
QR Microbiology
Mao, Xinru
Lee, Nung Kion
Saad, Shaban Eljali
Isabel, Fong Lim
Clinical translation for targeting DNA damage repair in non-small cell lung cancer: a review
description Despite significant advancements in screening, diagnosis, and treatment of non-small cell lung cancer (NSCLC), it remains the primary cause of cancer-related deaths globally. DNA damage is caused by the exposure to exogenous and endogenous factors and the correct functioning of DNA damage repair (DDR) is essential to maintain of normal cell circulation. The presence of genomic instability, which results from defective DDR, is a critical characteristic of cancer. The changes promote the accumulation of mutations, which are implicated in cancer cells, but these may be exploited for anti-cancer therapies. NSCLC has a distinct genomic profile compared to other tumors, making precision medicine essential for targeting actionable gene mutations. Although various treatment options for NSCLC exist including chemotherapy, targeted therapy, and immunotherapy, drug resistance inevitably arises. The identification of deleterious DDR mutations in 49.6% of NSCLC patients has led to the development of novel target therapies that have the potential to improve patient outcomes. Synthetic lethal treatment using poly (ADP-ribose) polymerase (PARP) inhibitors is a breakthrough in biomarker-driven therapy. Additionally, promising new compounds targeting DDR, such as ATR, CHK1, CHK2, DNA-PK, and WEE1, had demonstrated great potential for tumor selectivity. In this review, we provide an overview of DDR pathways and discuss the clinical translation of DDR inhibitors in NSCLC, including their application as single agents or in combination with chemotherapy, radiotherapy, and immunotherapy.
format Article
author Mao, Xinru
Lee, Nung Kion
Saad, Shaban Eljali
Isabel, Fong Lim
author_facet Mao, Xinru
Lee, Nung Kion
Saad, Shaban Eljali
Isabel, Fong Lim
author_sort Mao, Xinru
title Clinical translation for targeting DNA damage repair in non-small cell lung cancer: a review
title_short Clinical translation for targeting DNA damage repair in non-small cell lung cancer: a review
title_full Clinical translation for targeting DNA damage repair in non-small cell lung cancer: a review
title_fullStr Clinical translation for targeting DNA damage repair in non-small cell lung cancer: a review
title_full_unstemmed Clinical translation for targeting DNA damage repair in non-small cell lung cancer: a review
title_sort clinical translation for targeting dna damage repair in non-small cell lung cancer: a review
publisher AME Publishing Company
publishDate 2024
url http://ir.unimas.my/id/eprint/44449/2/Clinical.pdf
http://ir.unimas.my/id/eprint/44449/
https://tlcr.amegroups.org/article/view/83672/html
https://dx.doi.org/10.21037/tlcr-23-742
_version_ 1794644171549573120
score 13.211869

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