Targeting the DNA Repair Enzyme Polymerase θ in Cancer Therapy

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 sy...

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Veröffentlicht in:	Trends in Cancer 2021-02, Vol.7 (2), p.98-111
Hauptverfasser:	Schrempf, Anna, Slyskova, Jana, Loizou, Joanna I
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antineoplastic Combined Chemotherapy Protocols - pharmacology Antineoplastic Combined Chemotherapy Protocols - therapeutic use BRCA1 Protein - genetics BRCA1 Protein - metabolism BRCA2 Protein - genetics BRCA2 Protein - metabolism Cell Line, Tumor Disease Models, Animal DNA Breaks, Double-Stranded DNA Polymerase theta DNA Repair - drug effects DNA-Directed DNA Polymerase - metabolism Drug Development - trends Homologous Recombination - drug effects Humans Mice Molecular Targeted Therapy - methods Neoplasms - drug therapy Neoplasms - genetics Neoplasms - mortality Nucleic Acid Synthesis Inhibitors - pharmacology Nucleic Acid Synthesis Inhibitors - therapeutic use Prognosis Synthetic Lethal Mutations - drug effects
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Zusammenfassung:	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.
ISSN:	2405-8033 2405-8025
DOI:	10.1016/j.trecan.2020.09.007