Abstract A004: A novel viability and proliferation assay to enhance precision oncology
Authors: Chiara Maestri, Ivan Trus, Jahanvi Kumar, Rajeshwar Nitiyanandan, Ricardo Parker, William Cance, Christian Apfel
Journal: Cancer Research (2025)

Abstract Background The NCI MATCH trial has shown that only 1 out of 4 patients carry actionable driver mutations.1 Hence, functional precision medicine that leverages ex-vivo tumor models complementing genomic testing is experiencing a renaissance.2 Because most late-stage cancers tend to be heterogeneous and some anticancer drugs affect viability while others only inhibit proliferation, we have developed a novel multiplexed approach for simultaneously assessing cellular viability and proliferation of patient cancer tissues. Methods Using primary human cancer samples, we have developed an assay that uses cell and tissue aggregates that retain the tumor heterogeneity and microenvironment to measure viability (cytotoxicity) and proliferation (cytostasis) after treatment with NCCN-recommended therapies for specific cancer types with results within 10 days. Here, we report our results in four primary ovarian cancer samples that were treated for four days with a variety of therapeutics. The primary outcome measure was a difference score between the viability and proliferation dose-response curves. Results Overall, we found that the anti-proliferative effects occurred at a considerably lower concentration of drug than the anti-viability (cytotoxic) effects. The two readouts showed concordant results; for instance, for the folate antagonists methotrexate and pemetrexed that did not have cytostatic nor cytotoxic effects in any of the samples, while doxorubicin showed activities in both readouts in 2 out of the 4 tested samples. Furthermore, for certain drugs an anti-proliferative effect was detected without a cytotoxic effect; this phenomenon was observed for carboplatin, gemcitabine, and 5-FU in 3 out of 4 samples. Conclusions This assay reveals both cytotoxic and cytostatic responses of a patient's tumor to various drugs, providing critical guidance for personalized treatment selection in a short time frame. This dual-measurement approach is especially advantageous for limited or unique samples, enabling comprehensive testing from a single biological source. By distinguishing between cytotoxic and cytostatic drug effects, this method may optimize treatment for stable diseases, minimize patient exposure to ineffective drugs and potentially improve both survival and quality of life.1Flaherty et al. National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH). JCO 2020. 38:3883.2Letai et al. Functional precision cancer medicine—moving beyond pure genomics. Nature Med. 2017. 23(9): 1028. Citation Format: Chiara Maestri, Ivan Trus, Jahanvi Kumar, Rajeshwar Nitiyanandan, Ricardo Parker, William Cance, Christian Apfel. A novel viability and proliferation assay to enhance precision oncology [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr A004.