DNA repair and synthetic lethality |
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Authors: | Guo Gong-She Zhang Feng-Mei Gao Rui-Jie Delsite Robert Feng Zhi-Hui Powell Simon N |
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Institution: | 1. School of Public Health,Shandong University,Jinan 250012,China 2. Second People's Hospital of Weifang,Weifang 261041,China 3. Department of Radiation Oncology,Memorial Sloan Kettering Cancer Center,New York NY 10065,USA 4. School of Public Health,Shandong University,Jinan 250012,China;Department of Radiation Oncology,Washington University in St Louis,St Louis MO 63108,USA |
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Abstract: | Tumors often have DNA repair defects,suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality.Accumulating data demonstrate that DNA repair-defective tumors,in particular homologous recombination(HR),are highly sensitive to DNA-damaging agents.Thus,HR-defective tumors exhibit potential vulnerability to the synthetic lethality approach,which may lead to new therapeutic strategies.It is well known that poly(adenosine diphosphate(ADP)-ribose)polymerase(PARP)inhibitors show the synthetically lethal effect in tumors defective in BRCAI or BRCA2 genes encoded proteins that are required for efficient HR.In this review,we summarize the strategies of targeting DNA repair pathways and other DNA metabolic functions to cause synthetic lethality in HR-defective tumor cells. |
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Keywords: | DNA repair homologous recombination synthetic lethality BRCA Rad52 |
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