The influence of homologous recombination repair on temozolomide chemosensitivity in gliomas

Abstract Gliomas represent a prevalent form of primary brain tumors, with temozolomide (TMZ) serving as the established first-line therapeutic option. Nevertheless, the effectiveness of TMZ is hindered by the development of chemoresistance. Recent investigations have underscored the correlation of homologous recombination repair (HRR), a pivotal mechanism responsible for mending DNA double-strand breaks, with TMZ resistance in glioma treatment. This review centers on elucidating the significance of HRR in the management of gliomas, with a particular emphasis on pivotal molecules implicated in the HRR process, including RAD51, ATM, ATR, and newly identified small molecules that impact HRR. Modulating the expression of these genes can effectively restrain pathways such as ATM/CHK2, ATR/CHK1, and PI3K/AKT, subsequently augmenting the sensitivity of gliomas to TMZ. Noteworthy efforts have been directed towards exploring inhibitors of these pathways in recent research endeavors, culminating in encouraging outcomes. In conclusion, the involvement of HRR in glioma resistance unveils novel therapeutic avenues, with targeting crucial molecules in the HRR pathway, holding promise for enhancing the effectiveness of TMZ therapy.