What question did this study set out to answer?

The aim was to investigate the role of phospholipase D1 in platinum-resistant ovarian cancer and its potential as a therapeutic target.

April 5, 2026

Abstract 6492: Targeting phospholipase D1 overcomes platinum resistance and enhances cisplatin efficacy in ovarian cancer

Key Points

The aim was to investigate the role of phospholipase D1 in platinum-resistant ovarian cancer and its potential as a therapeutic target.
Evaluated PLD1 inhibition using OC cell lines and patient-derived tumor cells.
Conducted functional assays measuring various cancer cell behaviors like survival and invasiveness.
Assessed cisplatin responsiveness after PLD1 genetic knockdown or PLD1 inhibitor treatment.
Used xenograft and patient-derived xenograft models for in vivo studies.
PLD1 suppression led to reduced cell survival, proliferation, and invasiveness in resistant OC cells.
Induced apoptosis and increased DNA damage accumulation were observed.
PLD1 inhibition restored sensitivity to cisplatin across multiple resistant models.
Combined treatment with PLD1 inhibitor and cisplatin reduced tumor growth and extended survival in animal models.

Abstract

Abstract Background: Platinum-based chemotherapy is the standard treatment for high-grade serous ovarian cancer (HGSOC), yet the development of platinum resistance remains a major barrier to effective therapy. Phospholipase D1 (PLD1) has been implicated in tumor progression and stress response pathways, but its potential as a therapeutic target in platinum-resistant ovarian cancer (OC) has not been clearly defined. This study investigated whether targeting PLD1 can restore platinum sensitivity and improve therapeutic efficacy in resistant disease. Methods: The impact of PLD1 inhibition was evaluated using OC cell lines, patient-derived primary tumor cells, and both cell line-derived and patient-derived xenograft models. Functional assays measured clonogenic survival, proliferation, invasion, sphere formation, apoptosis, and DNA damage. Cisplatin responsiveness was assessed following genetic PLD1 knockdown or treatment with a PLD1 inhibitor. Results: PLD1 suppression significantly reduced survival, proliferation, and invasiveness in platinum-resistant OC cells, while inducing apoptosis and accumulation of DNA damage. Importantly, PLD1 inhibition restored cisplatin sensitivity across multiple resistant models, leading to a marked reduction in clonogenic survival. In vivo, combined PLD1 inhibition and cisplatin treatment markedly suppressed tumor growth, prolonged survival, and reduced metastatic burden in xenograft and PDX models, with greater therapeutic benefit observed in platinum-resistant tumors. Conclusions: PLD1 is a key survival determinant in platinum-resistant OC and contributes directly to treatment failure. Targeting PLD1 enhances the antitumor efficacy of cisplatin and provides strong preclinical rationale for PLD1-directed combination therapy in refractory HGSOC. Citation Format: Shin-Wha Lee, Sung Wan Kang, Dong Woo Kang, Yu-na Noh, Young-Jae Lee, Min-Seo Lee, Yong-Man Kim. Targeting phospholipase D1 overcomes platinum resistance and enhances cisplatin efficacy in ovarian cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6492.

Ask AI

Helpful

Bookmark