Directing the use of DDR kinase inhibitors in cancer treatment.
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ICR Authors
Authors
Brandsma, I
Fleuren, EDG
Williamson, CT
Lord, CJ
Fleuren, EDG
Williamson, CT
Lord, CJ
Document Type
Journal Article
Date
2017-12-01
Date Accepted
2017-10-04
Abstract
Defects in the DNA damage response (DDR) drive the development of cancer by fostering DNA mutation but also provide cancer-specific vulnerabilities that can be exploited therapeutically. The recent approval of three different PARP inhibitors for the treatment of ovarian cancer provides the impetus for further developing targeted inhibitors of many of the kinases involved in the DDR, including inhibitors of ATR, ATM, CHEK1, CHEK2, DNAPK and WEE1. Areas covered: We summarise the current stage of development of these novel DDR kinase inhibitors, and describe which predictive biomarkers might be exploited to direct their clinical use. Expert opinion: Novel DDR inhibitors present promising candidates in cancer treatment and have the potential to elicit synthetic lethal effects. In order to fully exploit their potential and maximize their utility, identifying highly penetrant predictive biomarkers of single agent and combinatorial DDR inhibitor sensitivity are critical. Identifying the optimal drug combination regimens that could used with DDR inhibitors is also a key objective.
Citation
Expert opinion on investigational drugs, 2017, 26 (12), pp. 1341 - 1355
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Source Title
Publisher
TAYLOR & FRANCIS LTD
ISSN
1354-3784
eISSN
1744-7658
Collections
Research Team
Gene Function