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Review
. 2021 Feb;7(2):98-111.
doi: 10.1016/j.trecan.2020.09.007. Epub 2020 Oct 24.

Targeting the DNA Repair Enzyme Polymerase θ in Cancer Therapy

Anna Schrempf  1 , Jana Slyskova  2 , Joanna I Loizou  3
Affiliations
Free article
Review

Targeting the DNA Repair Enzyme Polymerase θ in Cancer Therapy

Anna Schrempf et al. Trends Cancer. 2021 Feb.
Free article

Abstract

Targeted cancer therapies represent a milestone towards personalized treatment as they function via inhibition of cancer-specific alterations. Polymerase θ (POLQ), an error-prone translesion polymerase, also involved in DNA double-strand break (DSB) repair, is often upregulated in cancer. POLQ is synthetic lethal with various DNA repair genes, including known cancer drivers such as BRCA1/2, making it essential in homologous recombination-deficient cancers. Thus, POLQ represents a promising target in cancer therapy and efforts for the development of POLQ inhibitors are actively underway with first clinical trials due to start in 2021. This review summarizes the journey of POLQ from a backup DNA repair enzyme to a promising therapeutic target for cancer treatment.

Keywords: double-strand break repair; polymerase theta-mediated end joining; synthetic lethality; targeted cancer therapy.

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