Abstract 5995: Leveraging GPCR overexpression for personalized nanomedicine: A novel approach in ovarian cancer therapy

Background and Aims: Genetic heterogeneity in ovarian cancer drives frequent aberrant expression of cell surface proteins including G-protein coupled receptors (GPCRs), which harbour untapped potential for active targeting with nanomedicines. Our goal was to systematically identify GPCRs with significant overexpression in ovarian cancer biopsies and assessing their suitability to develop personalized GPCR-targeted nanomedicines for precise drug delivery. Methods: We ran a systematic analysis of public RNA-seq gene expression data, to reveal GPCRs with frequent overexpression in ovarian cancer tissues. To validate the relevance of initially identified receptors as targeting candidates, we confirmed their expression in six ovarian cancer cell lines and a selection of patient-derived samples (ascites derived tumour samples and solid tumours), using techniques such as RT-qPCR, flow cytometry, fluorescence imaging and immunofluorescence. This comprehensive analysis provided valuable insights into the prevalence and distribution of candidate receptors across different ovarian cancer probes. Furthermore, we utilized representative ovarian cancer cell lines as in vitro models to assess receptor-mediated cellular uptake and internalization processes, to further evaluate potential targets for nanoparticle delivery systems. Results: Analysis of public RNA-Seq datasets revealed 13 overexpressed GPCRs in cancer tissues compared to healthy tissues. Among these, we focused specifically on the coagulation factor II thrombin receptor (F2R) to highlight its intriguing potential as a therapeutic target. The variable expression of F2R was confirmed in both ovarian cancer cell lines and patient-derived samples. Furthermore, peptide binding to the receptor was successfully demonstrated using flow cytometry and fluorescent imaging, suggesting a promising approach for targeted drug delivery. Conclusions and Significance: Our findings underscore the importance of personalized targeting approaches in ovarian cancer therapy and highlight the potential of F2R as a promising therapeutic target. By integrating advanced molecular techniques with nanomedicine strategies, we strive to pave the way for more effective and tailored treatments for ovarian cancer patients. Citation Format: Riya Khetan, Preethi Eldi, Noor Lokman, Carmela Ricciardelli, Martin Oehler, Anton Blencowe, Katherine Pillman, Sanjay Garg, Hugo Albrecht. Leveraging GPCR overexpression for personalized nanomedicine: A novel approach in ovarian cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5995.