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dc.contributor.authorFoy, Victoria
dc.contributor.authorSchenk, Maximilian W
dc.contributor.authorBaker, Katie
dc.contributor.authorGomes, Fabio
dc.contributor.authorLallo, Alice
dc.contributor.authorFrese, Kristopher K
dc.contributor.authorForster, M
dc.contributor.authorDive, Caroline
dc.contributor.authorBlackhall, Fiona H
dc.date.accessioned2017-12-14T15:11:37Z
dc.date.available2017-12-14T15:11:37Z
dc.date.issued2017-12
dc.identifier.citationTargeting DNA damage in SCLC. 2017, 114:12-22 Lung Canceren
dc.identifier.issn1872-8332
dc.identifier.pmid29173760
dc.identifier.doi10.1016/j.lungcan.2017.10.006
dc.identifier.urihttp://hdl.handle.net/10541/620718
dc.description.abstractSCLC accounts for 15% of lung cancer worldwide. Characterised by early dissemination and rapid development of chemo-resistant disease, less than 5% of patients survive 5 years. Despite 3 decades of clinical trials there has been no change to the standard platinum and etoposide regimen for first line treatment developed in the 1970's. The exceptionally high number of genomic aberrations observed in SCLC combined with the characteristic rapid cellular proliferation results in accumulation of DNA damage and genomic instability. To flourish in this precarious genomic context, SCLC cells are reliant on functional DNA damage repair pathways and cell cycle checkpoints. Current cytotoxic drugs and radiotherapy treatments for SCLC have long been known to act by induction of DNA damage and the response of cancer cells to such damage determines treatment efficacy. Recent years have witnessed improved understanding of strategies to exploit DNA damage and repair mechanisms in order to increase treatment efficacy. This review will summarise the rationale to target DNA damage response in SCLC, the progress made in evaluating novel DDR inhibitors and highlight various ongoing challenges for their clinical development in this disease.
dc.language.isoenen
dc.rightsArchived with thanks to Lung cancer (Amsterdam, Netherlands)en
dc.titleTargeting DNA damage in SCLC.en
dc.typeArticleen
dc.contributor.departmentClinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester, UKClinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester, UKen
dc.identifier.journalLung Canceren
html.description.abstractSCLC accounts for 15% of lung cancer worldwide. Characterised by early dissemination and rapid development of chemo-resistant disease, less than 5% of patients survive 5 years. Despite 3 decades of clinical trials there has been no change to the standard platinum and etoposide regimen for first line treatment developed in the 1970's. The exceptionally high number of genomic aberrations observed in SCLC combined with the characteristic rapid cellular proliferation results in accumulation of DNA damage and genomic instability. To flourish in this precarious genomic context, SCLC cells are reliant on functional DNA damage repair pathways and cell cycle checkpoints. Current cytotoxic drugs and radiotherapy treatments for SCLC have long been known to act by induction of DNA damage and the response of cancer cells to such damage determines treatment efficacy. Recent years have witnessed improved understanding of strategies to exploit DNA damage and repair mechanisms in order to increase treatment efficacy. This review will summarise the rationale to target DNA damage response in SCLC, the progress made in evaluating novel DDR inhibitors and highlight various ongoing challenges for their clinical development in this disease.


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