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Synthetic Lethality Targeting Polθ.

Authors :
Drzewiecka M
Barszczewska-Pietraszek G
Czarny P
Skorski T
Śliwiński T
Source :
Genes [Genes (Basel)] 2022 Jun 20; Vol. 13 (6). Date of Electronic Publication: 2022 Jun 20.
Publication Year :
2022

Abstract

Research studies regarding synthetic lethality (SL) in human cells are primarily motivated by the potential of this phenomenon to be an effective, but at the same time, safe to the patient's anti-cancer chemotherapy. Among the factors that are targets for the induction of the synthetic lethality effect, those involved in DNA repair seem to be the most relevant. Specifically, when mutation in one of the canonical DNA double-strand break (DSB) repair pathways occurs, which is a frequent event in cancer cells, the alternative pathways may be a promising target for the elimination of abnormal cells. Currently, inhibiting RAD52 and/or PARP1 in the tumor cells that are deficient in the canonical repair pathways has been the potential target for inducing the effect of synthetic lethality. Unfortunately, the development of resistance to commonly used PARP1 inhibitors (PARPi) represents the greatest obstacle to working out a successful treatment protocol. DNA polymerase theta (Polθ), encoded by the POLQ gene, plays a key role in an alternative DSB repair pathway-theta-mediated end joining (TMEJ). Thus, it is a promising target in the treatment of tumors harboring deficiencies in homologous recombination repair (HRR), where its inhibition can induce SL. In this review, the authors discuss the current state of knowledge on Polθ as a potential target for synthetic lethality-based anticancer therapies.

Details

Language :
English
ISSN :
2073-4425
Volume :
13
Issue :
6
Database :
MEDLINE
Journal :
Genes
Publication Type :
Academic Journal
Accession number :
35741863
Full Text :
https://doi.org/10.3390/genes13061101