Targeting DNA repair pathways for cancer treatment: what's new?

被引:151
作者
Kelley, Mark R. [1 ,2 ,3 ,4 ]
Logsdon, Derek [2 ]
Fishel, Melissa L. [1 ,2 ]
机构
[1] Indiana Univ Sch Med, Herman B Wells Ctr Pediat Res, Dept Pediat, Indianapolis, IN 46202 USA
[2] Indiana Univ Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA
[3] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA
[4] Herman B Wells Ctr Pediat Res, Indianapolis, IN 46202 USA
关键词
clinical trials; DNA repair inhibition; DNA repair pathways; DNA repair targets; small-molecule inhibitors; SMALL-MOLECULE INHIBITORS; STRAND BREAK REPAIR; NUCLEOTIDE EXCISION-REPAIR; HOMOLOGOUS RECOMBINATION; PARP INHIBITORS; APURINIC/APYRIMIDINIC ENDONUCLEASE; CLINICAL DEVELOPMENT; POTENT INHIBITOR; MISMATCH REPAIR; DAMAGE;
D O I
10.2217/fon.14.60
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Disruptions in DNA repair pathways predispose cells to accumulating DNA damage. A growing body of evidence indicates that tumors accumulate progressively more mutations in DNA repair proteins as cancers progress. DNA repair mechanisms greatly affect the response to cytotoxic treatments, so understanding those mechanisms and finding ways to turn dysregulated repair processes against themselves to induce tumor death is the goal of all DNA repair inhibition efforts. Inhibition may be direct or indirect. This burgeoning field of research is replete with promise and challenge, as more intricacies of each repair pathway are discovered. In an era of increasing concern about healthcare costs, use of DNA repair inhibitors can prove to be highly effective stewardship of R&D resources and patient expenses.
引用
收藏
页码:1215 / 1237
页数:23
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