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Targeting DNA damage in SCLC

Foy, V; Schenk, MW; Baker, K; Gomes, F; Lallo, A; Frese, KK; Forster, M; ... Blackhall, F; + view all (2017) Targeting DNA damage in SCLC. [Review]. Lung Cancer , 114 pp. 12-22. 10.1016/j.lungcan.2017.10.006. Green open access

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Abstract

SCLC 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.

Type: Article
Title: Targeting DNA damage in SCLC
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.lungcan.2017.10.006
Publisher version: http://doi.org/10.1016/j.lungcan.2017.10.006
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Lung Cancer, Small Cell Lung Cancer, DNA Repair Pathways, PARP Inhibitors, Checkpoint Inhibitors
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10050170
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