RECQL1 as a potential therapeutic target for PARP inhibitor-resistant ovarian cancer

Overcoming resistance to poly (ADP-ribose) polymerase (PARP) inhibitors is an urgent challenge for ovarian cancer treatment. Here, we investigated RECQL1, a RecQ helicase involved in homologous recombination repair, as a potential target for overcoming PARP inhibitor resistance in this disease. Patients with platinum-sensitive recurrent ovarian cancer treated with the PARP inhibitor olaparib between March 2018 and December 2021 were included. Immunohistochemistry assays were conducted to assess RECQL1 protein expression patterns in surgically resected ovarian cancer tissues. The effect of RECQL1 knockdown on olaparib resistance was evaluated in vitro using ovarian cancer cells transfected with an anti-RECQL1 siRNA. Among 44 patients, those with no response to olaparib had significantly higher RECQL1 expression levels compared with responders (P = 0.020). Kaplan-Meier curves showed significantly shorter overall survival in the high RECQL1 expression group than in the low expression group (median, 26.0 months vs. not reached; P = 0.027). Multivariate analysis revealed high RECQL1 expression to be a significant prognostic factor for shorter overall survival (P = 0.036). RECQL1 knockdown significantly enhanced the sensitivity to olaparib in two ovarian cancer cell lines. Overall, RECQL1 plays a critical role in PARP inhibitor resistance and is a promising therapeutic target to improve ovarian cancer patient outcomes.