Directing the use of DDR kinase inhibitors in cancer treatment.

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Authors

Brandsma, I
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

Rights

Source Title

Publisher

TAYLOR & FRANCIS LTD

ISSN

1354-3784

eISSN

1744-7658

Research Team

Gene Function

Notes