Recent Developments Using Small Molecules to Target RAD51: How to Best Modulate RAD51 for Anticancer Therapy?

被引：38

作者：

Budke, Brian ^{[1
]}

Lv, Wei ^{[2
]}

Kozikowski, Alan P. ^{[2
]}

Connell, Philip P. ^{[1
]}

机构：

[1] Univ Chicago, Dept Radiat & Cellular Oncol, 5841 S Maryland Ave, Chicago, IL 60637 USA

[2] Univ Illinois, Dept Med Chem & Pharmacognosy, Drug Discovery Program, 833 S Wood St, Chicago, IL 60612 USA

来源：

CHEMMEDCHEM | 2016年 / 11卷 / 22期

关键词：

cancer therapy; drug discovery; homologous recombination; medicinal chemistry; RAD51; HOMOLOGOUS RECOMBINATIONAL REPAIR; SINGLE-STRANDED-DNA; END-JOINING REPAIR; TUMOR-CELLS; SACCHAROMYCES-CEREVISIAE; CHROMOSOME STABILITY; IONIZING-RADIATION; CHEMICAL-COMPOUND; MAMMALIAN-CELLS; MARINE SPONGE;

D O I：

10.1002/cmdc.201600426

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Homologous recombination (HR) is an evolutionarily conserved DNA repair process. Overexpression of the key HR protein RAD51 is a common feature of malignant cells. RAD51 plays two distinct genome-stabilizing roles, including HR-mediated repair of double-strand breaks (DSBs) and the promotion of replication fork stability during replication stress. Because upregulation of RAD51 in cancer cells can promote tumor resistance to DNA-damaging oncologic therapies, we and others have worked to develop cancer therapeutics that target various aspects of RAD51 protein function. Herein, we provide an overview of recent developments in this field, together with our perspectives on the challenges associated with these evolving anticancer strategies.

引用

页码：2468 / 2473

页数：6

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