Abstract P104: Exploring the Therapeutic Potential of a Novel Peptide Targeting Lysophosphatidic Acid Receptor-3 (LPAR3) in Ovarian Cancer

Abstract Background: Lysophosphatidic acid (LPA), an onco-lipid, is reported to be elevated in the tumour microenvironment in ovarian cancer. The binding of LPA to its cognate receptor LPAR3 leads to the activation of the MAPK, PI3K signalling pathways, resulting in the proliferation, invasion, and metastasis. New generation drugs have been advocated to combat ovarian cancer, but have not scored much over chemotherapy. Our study identified LPAR3 binding peptides that may hinder the LPA-LPAR3 interaction, thereby delaying ovarian cancer progression. The peptides may be used as an adjunct therapy along with chemotherapy. Objectives: To identify, characterise, and validate the LPAR3 binding peptides Methodology: The LPAR3 binding peptides were identified by in-vitro panning using the PhD-12 phage display peptide library. Three rounds of in-vitro panning were carried out to enrich the phages, followed by NGS sequencing to decode the peptide sequence. The peptides were synthesised, and the secondary structures were identified by CD spectroscopy. The specificity of the LPAR3 binding phages and the peptides was confirmed by phage ELISA, confocal microscopy, and flow cytometry. Results: The novel LPAR3 binding peptides were identified using the in-vitro panning. After NGS analysis, the frequency count of the 12-mer peptide (Pep-1) XQMXXXYXQSXX was highest, followed by (Pep-2) XHXAXXLGXVXX and (Pep-3) XXDWXXSPXXAX. The peptides were synthesized, and characterization confirmed the beta secondary structures, suggesting the structural stability of the peptides. The phage and cell-based ELISA confirmed the specificity of the LPAR3 Pep1 phages to rLPAR3 and the ovarian cancer cell line, OVCAR3, respectively. The specificity of the peptides to the OVCAR3 was confirmed by confocal microscopy and flow cytometry. Conclusion: The novel LPAR3 binding peptides were identified and validated for their specificity to the human ovarian cancer cells and may be used as adjunct therapy along with chemotherapy to combat the ovarian cancer progression. Citation Format: Bhavana Bhat, Yugandhara Jirwankar, Vikas Dighe. Exploring the Therapeutic Potential of a Novel Peptide Targeting Lysophosphatidic Acid Receptor-3 (LPAR3) in Ovarian Cancer [abstract]. In: Proceedings of Frontiers in Cancer Science 2025; 2025 Nov 5-7; Singapore. Philadelphia (PA): AACR; Cancer Res 2026;86(13_Suppl):Abstract nr P104.