Targeting the DNA Repair Enzyme Polymerase θ in Cancer Therapy.

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.

• Authors: Anna Schrempf, Jana Slyskova, Joanna I Loizou
• Journal: Trends in cancer (Trends Cancer) Vol. 7 Issue 2 Pg. 98-111 (02 2021) ISSN: 2405-8025 [Electronic] United States
• PMID: 33109489 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• BRCA1 Protein
• BRCA1 protein, human
• BRCA2 Protein
• BRCA2 protein, human
• Nucleic Acid Synthesis Inhibitors
• DNA polymerase theta
• DNA-Directed DNA Polymerase

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• BRCA1 Protein (genetics, metabolism)
• BRCA2 Protein (genetics, metabolism)
• Cell Line, Tumor
• DNA Breaks, Double-Stranded
• DNA Repair (drug effects)
• DNA-Directed DNA Polymerase (metabolism)
• Disease Models, Animal
• Drug Development (trends)
• Homologous Recombination (drug effects)
• Humans
• Mice
• Molecular Targeted Therapy (methods)
• Neoplasms (drug therapy, genetics, mortality)
• Nucleic Acid Synthesis Inhibitors (pharmacology, therapeutic use)
• Prognosis
• Synthetic Lethal Mutations (drug effects)