Abstract 3153: An integrated <i>in vitro</i> profiling platform for the simultaneous assessment of anti cancer efficacy and multi organ toxicity

Abstract The high attrition rate of oncology drug candidates is frequently driven by an insufficient understanding of a compound's therapeutic index early in development. Many promising molecules advance based on potent efficacy, only to fail later due to unanticipated safety concerns. To address this, there is a critical need for a comprehensive in vitro strategy that can simultaneously and systematically evaluate anti-cancer activity and organ-specific toxicity risks in the preclinical phase, enabling more informed and de-risked candidate selection. To address this gap, we developed an integrated in vitro profiling platform that synergizes a robust Efficacy &amp; Mechanism Module with an extensive Early Safety &amp; Toxicity Module. The efficacy module delivers a multi-faceted assessment of anti-tumor potential, beginning with high-throughput viability screening across a diverse panel of human cancer cell lines to determine potency and selectivity. It can be further implemented by functional phenotyping assays including angiogenesis, migration, and invasion to evaluate anti-metastatic potential. Furthermore, downstream molecular investigations via qPCR and Western Blot analysis elucidate mechanisms of action and target engagement. The safety module employs a battery of specialized assays in relevant normal cell models to proactively identify a broad spectrum of adverse effects, encompassing organ-specific toxicities such as hepatotoxicity, nephrotoxicity, cardiotoxicity, and neurotoxicity, alongside general toxicological concerns including mitochondrial toxicity, genotoxicity, and phototoxicity. By integrating these rich datasets, our platform empowering the selection of safer and more effective lead compounds for successful translational development. Citation Format: Xia Tu,Hao Wen,Dawei Yan,Jingna Ren,Qin Guo,Peichuan Zhang,Haiheng Dong. An integrated in vitro profiling platform for the simultaneous assessment of anti cancer efficacy and multi organ toxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3153.