Targeting Polymerase Theta (POLθ) for Cancer Therapy

Overview

Journal Cancer Treat Res

Publisher Springer

Specialties Oncology
Pharmacology

Date 2023 Nov 17

PMID 37978141

Authors

Jeffrey Patterson-Fortin

Alan D DAndrea

Affiliations

Soon will be listed here.

Abstract

Polymerase theta (POLθ) is the critical multi-domain enzyme in microhomology-mediated end-joining DNA double-stranded break repair. POLθ is expressed at low levels in normal tissue but is often overexpressed in cancers, especially in DNA repair deficient cancers, such as homologous-recombination cancers, rendering them exquisitely sensitive to POLθ inhibition secondary to synthetic lethality. Development of POLθ inhibitors is an active area of investigation with inhibitors of the N-terminal helicase domain or the C-terminal polymerase domain currently in clinical trial. Here, we review POLθ-mediated microhomology-mediated end-joining, the development of POLθ inhibitors, and the potential clinical uses of POLθ inhibitors.

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