Polθ (140)

DNA polymerase theta is a distinctive, large (290 kDa) multifunctional A-family DNA polymerase essential for DSB repair via the MMEJ pathway. It participates in error-prone DNA repair processes, such as double-strand break repair and interstrand crosslink repair. While Polθ expression is minimal in normal cells, it is significantly upregulated in breast, lung, and ovarian cancers. Inhibitors targeting Polθ have been developed to block its enzymatic activity and disrupt DNA repair, showing potential in sensitizing cancer cells to DNA-damaging agents and improving therapeutic outcomes. Combining Polθ inhibitors with other DNA repair or checkpoint inhibitors has also yielded synergistic effects. Research into Polθ as a therapeutic target and the development of its inhibitors offer a promising direction for advancing cancer treatments.