Abstract 6772: Heterogeneity of <i>ex-vivo</i> tumor responses in primary ovarian cancer tissues

Abstract Background: While most stage III and IV ovarian cancer patients respond to neo-adjuvant carboplatin and paclitaxel, not all do. Some experience recurrence within 6 months (platinum-resistant), others after 6 months, and a minority achieve remission beyond 5 years. Apart from BRCA mutations, genomic testing offers little guidance on patient-to-patient heterogeneity in tumor responses. To address this, we developed an internally validated functional profiling platform in a CLIA-certified and CMS accredited lab. Our goal was to measure in-vitro heterogeneity of tumor responses to NCCN-recommended treatments to identify the most suitable therapies for patients. Methods: Ovarian cancer biopsies were shipped overnight and processed the same day using our proprietary functional profiling platform in a physiological culture system with around 2, 000 viable cells per well. Tissues were exposed to up to 24 NCCN recommended therapies on the day after for 4 days, cytotoxicity readout with dose response curves within 7 days. Heterogeneity was assessed by the interquartile ratios of the EC50 drug concentrations. Not requiring organoid-like cell growth offers two advantages: a) actionable results for almost all patients and b) a fast turnaround time with an issued report within 10 days. Heterogeneity was evaluated using interquartile ratios of EC50 drug concentrations. Results: A total of 17 ovarian cancer tissues were processed and exposed to up to 24 NCCN recommended therapies. Interquartile ratios (IQRs) of carboplatin and paclitaxel were 3.62 and 5.22 for the individual drugs, the IQR for the carboplatin/paclitaxel combination was 91.1, suggestive for synergy between both drugs in some, but not other cancer tissues. Gemcitabine’s and cisplatin/gemcitabine IQRs were 39.8 and 17.9, respectively, suggestive that patient benefits to gemcitabine or platinum/gemcitabine combination may vary greatly. IQRs for doxorubicin and olaparib were only 5.8 and 3.2, owing to many tissues not showing any tumor response. All p-value comparisons for EC EC50s heterogeneity of tumor responses were &amp;lt;0.001. Conclusions: Consistent with the clinically known patient-to-patient heterogeneity of tumor responses, such heterogeneities were also observed in our in-vitro tissue culture platform. Thus, these results warrant external validation of this already internally validated laboratory developed test (LDT). Citation Format: Chiara Maestri, Ivan Trus, Rajeshwar Nitiyanandan, Jahanvi Kumar, Ricardo J. Parker, William Cance, Christian Apfel. Heterogeneity of ex-vivo tumor responses in primary ovarian cancer tissues [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 6772.