DNA repair and synthetic lethality.
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 BRCA1 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.
School of Public Health, Shandong University, Jinan 250012, China.
Gong-She
GS
Guo
Feng-Mei
FM
Zhang
Rui-Jie
RJ
Gao
Robert
R
Delsite
Zhi-Hui
ZH
Feng
Simon N
SN
Powell
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005804:Genes, Lethal / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000187:drug effects; D018816:Genes, cdc / Q000187:drug effects; D006801:Humans; D016296:Mutagenesis; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051721:Rad52 DNA Repair and Recombination Protein / Q000037:antagonists & inhibitors; D011995:Recombination, Genetic / Q000187:drug effects / Q000235:genetics
D000970:Antineoplastic Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051721:Rad52 DNA Repair and Recombination Protein