Cancer Biology and Therapy · Published 2026-07-28 · DOI 10.1080/15384047.2026.2703892
Bo Zhou, Zhixin Wang, Jun Qi, Fengke Liang, Haohui Liu, Yunqi Li
DNA double-strand breaks (DSBs) are the most severe DNA damage, and defective repair can lead to apoptosis or malignant transformation. DSBs are mainly repaired by nonhomologous end joining (NHEJ) and homologous recombination (HR), while microhomology-mediated end joining (MMEJ) serves as a backup pathway. Since DNA polymerase theta (Polθ) is essential for MMEJ, this pathway is also named Polθ-mediated end joining. Polθ is barely expressed in normal tissues but overexpressed in many cancers, making it a promising therapeutic target. In recent years, Polθ inhibitors and related therapeutic strategies have emerged rapidly, with clinical trials underway. This review summarizes the structure, function and expression of Polθ in tumorigenesis, highlights synthetic lethal strategies, drug development and clinical translation, and discusses current limitations and future directions for cancer research.
Abstract from DOAJ. Public domain (CC0 1.0).
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Zhou, B., Wang, Z., Qi, J., et al. (2026). DNA polymerase theta (Polθ): a novel candidate for targeted cancer therapy. Cancer Biology and Therapy. https://doi.org/10.1080/15384047.2026.2703892