Abstract 5172: Mechanistic insights into PLK1 target inhibition in ovarian cancer: Functional suppression and PROTAC-based therapeutic agents

Abstract OBJECTIVE: This study aimed to identify the oncogenic role of PLK1(Polo-like kinase 1) in ovarian cancer and evaluate its potential as a PROTAC therapeutic target candidate. We also investigated the change in the functional properties of cancer by PLK1 inhibition and whether it is possible to improve cell viability rate through PROTAC-based PLK1 protein degradation. METHODS: Functional studies were conducted using PLK1 siRNA in SKOV3 cell lines. Changes in cell proliferation, migration, invasion, and wound-healing ability were evaluated following PLK1 silencing. Quantitative RT-PCR was used to measure PLK1 expression in cell lines and in benign, malignant ovarian tumor tissue samples.In addition, we evaluated the effect on sensitivity in ovarian cancer cell lines and paclitaxel-resistant ovarian cancer cell lines using PLK1 target PROTAC. RESULTS: Expression of PLK1 at the RNA level is significantly overexpressed in ovarian cancer cells compared to normal cells. Also, PLK1 expression was significantly overexpressed in malignant ovarian tumor compared to benign ovarian neoplasm. PLK1 silencing significantly reduced cell proliferation and decreased migration and invasion by 50-60%. Cell viability assays performed in both parental and paclitaxel-resistant ovarian cancer cell lines demonstrated that treatment with the PLK1-targeting PROTAC resulted in a significantly higher level of cell death compared to paclitaxel. CONCLUSION: Our results demonstrate that PLK1 inhibition at both the RNA and protein levels suppresses the metastatic characteristics of ovarian cancer and highlights its potential as a therapeutic target. Targeting PLK1 in ovarian cancer may contribute to the inhibition of metastatic aibilty and the overcoming of chemoresistance. Citation Format: jaesung Ryu, Baek MooJun, HyoWook Gil, Eunjung Yang, Kwangseock Kim, Taewan Kim, Kong Hyejeong, Beamjun Park, Jeong Kyu Bang, Seob Jeon. Mechanistic insights into PLK1 target inhibition in ovarian cancer: Functional suppression and PROTAC-based therapeutic agents [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 5172.