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Updated: Jan 12, 2026

Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays
Published on: February 24, 2023
RECQL1 as a potential therapeutic target for PARP inhibitor-resistant ovarian cancer
Hiroyuki Yoshida1, Jiarui Li2, Hiroaki Inui3
1Department of Gynecologic Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan. hiro_y@saitama-med.ac.jp.
Abstract:
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.
Insights
High RECQL1 expression correlates with poor response to olaparib in ovarian cancer. Targeting RECQL1 may overcome poly (ADP-ribose) polymerase inhibitor resistance, improving patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ovarian cancer treatment faces challenges with resistance to poly (ADP-ribose) polymerase (PARP) inhibitors.
- Understanding mechanisms of resistance is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the role of RECQL1, a RecQ helicase, in overcoming PARP inhibitor resistance in ovarian cancer.
- To evaluate RECQL1 as a potential therapeutic target.
Main Methods:
- Assessed RECQL1 protein expression via immunohistochemistry in 44 ovarian cancer patients treated with olaparib.
- Evaluated the effect of RECQL1 knockdown using siRNA in vitro.
- Performed Kaplan-Meier and multivariate analyses for survival outcomes.
Main Results:
- Patients with no response to olaparib showed significantly higher RECQL1 expression (P=0.020).
- High RECQL1 expression was linked to shorter overall survival (P=0.027) and was a significant prognostic factor (P=0.036).
- RECQL1 knockdown enhanced sensitivity to olaparib in ovarian cancer cell lines.
Conclusions:
- RECQL1 is critically involved in PARP inhibitor resistance in ovarian cancer.
- RECQL1 represents a promising therapeutic target to improve treatment efficacy and patient outcomes.
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