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Targeting Polymerase Theta (POLθ) for Cancer Therapy

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Targeting the DNA Damage Response for Cancer Therapy

Part of the book series: Cancer Treatment and Research ((CTAR,volume 186))

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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Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA

    Jeffrey Patterson-Fortin

  2. Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA

    Jeffrey Patterson-Fortin & Alan D. D’Andrea

  3. Harvard Medical School, Center for DNA Damage and Repair, Susan F. Smith Center for Women’s Cancers (SFSCWC), The Fuller-American Cancer Society, Dana-Farber Cancer Institute, HIM 243, 450 Brookline Ave., Boston, MA, 02215, USA

    Alan D. D’Andrea

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Correspondence to Alan D. D’Andrea .

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Editors and Affiliations

  1. The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Timothy A. Yap

  2. Dana-Farber Cancer Institute, Boston, MA, USA

    Geoffrey I. Shapiro

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Patterson-Fortin, J., D’Andrea, A.D. (2023). Targeting Polymerase Theta (POLθ) for Cancer Therapy. In: Yap, T.A., Shapiro, G.I. (eds) Targeting the DNA Damage Response for Cancer Therapy. Cancer Treatment and Research, vol 186. Springer, Cham. https://doi.org/10.1007/978-3-031-30065-3_15

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