Abstract 2804: 3D printing of perfusable alveolar model for efficacy evaluation of polyisoprenylated cysteinyl amide inhibitors on lung cancer cells

Abstract Lung cancer is the leading cause of cancer death in the United States, and Black Americans are being disproportionality affected. Lung adenocarcinoma (LUAD) is the most common histological lung cancer subtype among all lung cancer patients, including black patients. There is still no available physiologically relevant three-dimensional (3D) in vitro model that can be used to study the treatment efficacy on LUAD cells, in particular, those from Black patients. In this study, we aim to develop a 3D alveolar model with a perfusable epithelialized channel using 3D biofabrication technologies. We will apply the model to test their efficacies of polyisoprenylated cysteinyl amide inhibitors (PCAIs) and other drugs on LUAD. First, a perfusable channel is constructed within a gelatin composite extracellular matrix (ECM) using a sacrificial material-assisted 3D embedded printing technology. Next, the channel is seeded with KRAS-mutated NCI-H23 LUAD (derived from a Black patient) or hAEC-C7 (untransformed, immortalized human alveolar epithelial cells) respectively, and exposed to drugs to test the anti-cancer efficacy. In particular, PCAIs, which are potential therapeutics targeting activated KRAS, are investigated for their cytotoxicity on H23 LUAD and hAEC-C7 cells for comparison. Compared to two-dimensional (2D) models, the proposed 3D alveolar model can offer a more physiologically relevant 3D cell-to-ECM environment to test LUAD therapeutics. The use of H23 cells and, in the future, other LUAD cells from Black patients ensures that any developed drugs constitute valid treatment options for black patients with RAS-mutated pathways, thus minimizing health disparities. Citation Format: Diana Isabel Romero, Bing Ren, Christopher Leon, Ite A. Offringa, Nazarius S. Lamango, Yong Huang. 3D printing of perfusable alveolar model for efficacy evaluation of polyisoprenylated cysteinyl amide inhibitors on lung cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2804.