Abstract 4234: Synergistic anti-proliferative effects of JIN-001, a novel HSP90 selective inhibitor, in combination with platinum-based drugs in ovarian cancer cell lines

Abstract Introduction: Heat shock proteins (HSPs) have been considered as a promising therapeutic target for ovarian cancer (OC), the most lethal gynecologic malignancy. HSPs facilitate tumor cell adaptation to short-term stress, promoting the development of more malignant phenotypes and the acquisition of resistance to therapeutic treatments over time. To date, Clinical trials of HSP90 inhibitors have shown modest benefits in advanced cancer patients, with no sufficient efficacy as monotherapy. Here, We investigated the anti-proliferative effects of JIN-001, a selective HSP90i, combined with platinum-based drugs in OC cell lines. Material and methods: We examined the co-treatment effects of JIN-001 and paclitaxel (PTX) or cisplatin (Cis, platinum-based) on viability in OC cell lines (OV90, TOV21G, and OVCAR3) and drug-resistance sublines (OV90/PTX200, TOV21G/PTX100, and OVCAR3-CisR). Drug-resistant OC sublines were generated by gradually exposing OC cells to increasing concentrations of PTX or Cis. Each drug was tested either for monotherapy or in 1:1 ratio combination. Also, we assessed the synergistic anti-proliferative effects of JIN-001 (0.1 or 0.05 μM) with Cis on OVCAR3 and OVCAR3-CisR. Results: Co-treatment of JIN-001 with PTX or Cis reduced IC50 in drug-resistant OC sublines compared to PTX or Cis alone. The IC50 of JIN-001 at a fixed dose in combination with Cis were lower in the OVACAR3 and OVCAR-CisR, compared to the single treatment. IC50 (μM) are shown below. Conclusion: The combination of JIN-001 with PTX or Cis enhanced anti-proliferative effects and reduced IC50 in OC cell lines and drug-resistant sublines compared to monotherapy. This suggests JIN-001’s potential as a combination therapy with platinum-based drugs in OC patients. Further studies are needed to examine whether the combination therapy of JIN-001 and the conventional drugs decelerates the tumor’s ability to adapt and develop drug resistance. Citation Format: Jue Young Kim, Ha-Yeon Shin, Anna Jo, Ethan Seah, Choonok Kim, Jae-Hoon Kim. Synergistic anti-proliferative effects of JIN-001, a novel HSP90 selective inhibitor, in combination with platinum-based drugs in ovarian cancer cell lines [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 4234.