Directing the use of DDR kinase inhibitors in cancer treatment.
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Date
2017-12-01ICR Author
Author
Brandsma, I
Fleuren, EDG
Williamson, CT
Lord, CJ
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Animals
Humans
Neoplasms
DNA Damage
Antineoplastic Agents
Protein Kinase Inhibitors
Drug Design
Mutation
Molecular Targeted Therapy
Biomarkers
Poly(ADP-ribose) Polymerase Inhibitors
Research team
Gene Function
Language
eng
Date accepted
2017-10-04
License start date
2017-12
Citation
Expert opinion on investigational drugs, 2017, 26 (12), pp. 1341 - 1355
Publisher
TAYLOR & FRANCIS LTD