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Toma M , Sullivan-Reed K , Sliwinski T , Skorski T
RAD52 as a Potential Target for Synthetic Lethality-Based Anticancer Therapies
Cancers (Basel). 2019 Oct 14;11(10)
PMID: 31615159    PMCID: PMC6827130    URL: https://www.ncbi.nlm.nih.gov/pubmed/31615159
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Alterations in DNA repair systems play a key role in the induction and progression of cancer. Tumor-specific defects in DNA repair mechanisms and activation of alternative repair routes create the opportunity to employ a phenomenon called "synthetic lethality" to eliminate cancer cells. Targeting the backup pathways may amplify endogenous and drug-induced DNA damage and lead to specific eradication of cancer cells. So far, the synthetic lethal interaction between BRCA1/2 and PARP1 has been successfully applied as an anticancer treatment. Although PARP1 constitutes a promising target in the treatment of tumors harboring deficiencies in BRCA1/2-mediated homologous recombination (HR), some tumor cells survive, resulting in disease relapse. It has been suggested that alternative RAD52-mediated HR can protect BRCA1/2-deficient cells from the accumulation of DNA damage and the synthetic lethal effect of PARPi. Thus, simultaneous inhibition of RAD52 and PARP1 might result in a robust dual synthetic lethality, effectively eradicating BRCA1/2-deficient tumor cells. In this review, we will discuss the role of RAD52 and its potential application in synthetic lethality-based anticancer therapies.
Toma, Monika Sullivan-Reed, Katherine Sliwinski, Tomasz Skorski, Tomasz R01 CA186238/NH/NIH HHS/United States Translational Research Program award 6565-19/Leukemia and Lymphoma Society doctoral scholarship Etiuda6 DEC-2018/28/T/NZ7/00105/Polish National Science Center 2016/22/M/NZ7/00375/Narodowe Centrum Nauki Journal Article Review Switzerland Cancers (Basel). 2019 Oct 14;11(10). pii: cancers11101561. doi: 10.3390/cancers11101561.