Abstract C052: Preclinical evaluation of therapeutics in gastric cancer using diverse patient-derived models

Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide, with Latinos in the U.S. experiencing higher incidence and poorer survival rates compared to non-Latino whites (NLW). Current molecular characterization efforts, such as The Cancer Genome Atlas (TCGA), lack data on Latino patients, with only 2% of samples from Latino ancestry. To address this gap, the University of California Minority Patient-Derived Xenograft (PDX) Development and Trial Center (UCaMP) and The University of California and the University of Texas Southwestern (UCaTS) Diversity Patient-Derived Xenograft (PDX) Development and Trial Center are developing preclinical models (PDXs and organoids) from diverse populations to identify new drug targets for GC. We have successfully developed 37 preclinical models, reflecting a 44% success rate from 84 GC patients. These models represent diverse backgrounds: 14% Asian, 14% Black or African American, 5% Native Hawaiian or Pacific Islander, 22% NLW, 35% Hispanic or Latino, and 4% Not Reported. Currently, we are characterizing these models genomically and testing their vulnerability to 27 FDA-approved/NCI-CTEP inhibitors. Initial results from 15 models show the highest response to the pan-PI3K inhibitor copanlisib and the anthracycline epirubicin. We have also investigated PARP inhibitors (PARPi), given their success in breast and ovarian tumors. PARPi efficacy in GC ranged across models, with some showing sensitivity, others intermediate response, and some limited response. Next, we evaluated whether PARPi efficacy could be increased when combined with standard chemotherapies in the intermediate- and limited-response GC models. Notably, PARPi Talazoparib demonstrated synergy with epirubicin, as determined by the BLISS model. Ongoing work focuses on understanding this synergy and identifying biomarkers for PARPi response, which could help predict treatment outcomes in GC patients. Our research aims to uncover new drug targets for GC and provide preclinical evidence for their potential efficacy. Citation Format: Leslie Cuellar-Vite, Hongyong Zhang, Nicole B. Halmai, Ana Estrada-Florez, Jasmine Diaz, Paul C. Lott, Dennis J. Montoya, UCaMP Consortium, UCaTS Consortium, Luis G. Carvajal-Carmona. Preclinical evaluation of therapeutics in gastric cancer using diverse patient-derived models [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C052.