Abstract 4038: Study of therapeutic effects of polyisoprenylated cysteinyl amide inhibitors on lung cancer cells of black patients using 3D-Printed alveolar model

• Published in: Cancer research (Chicago, Ill.) Ill.), 2022-06, Vol.82 (12_Supplement), p.4038-4038
• Main Authors: Belony, Nadine, Ren, Bing, Pham, Phuc, Gregory, Matthew, Puente, Pablo E., Lamango, Nazarius S., Offringa, Ite A., Huang, Yong
• Format: Article
• Language: English
• ISSN: 1538-7445; 1538-7445
• DOI: 10.1158/1538-7445.AM2022-4038

Lung cancer is one of the top five deadliest cancers, and black Americans have a higher mortality rate when compared to white Americans even though they smoke relatively fewer cigarettes. Lung adenocarcinoma (LUAD) is the most common histological lung cancer subtype in all population groups including blacks. There are no in vitro model systems to study lung cancer in black subjects, and there is only one lung adenocarcinoma cell line from a black patient (NCI-H23). Here we aim to address the lack of in vitro models to study black LUAD. Using three-dimensional (3D) biofabrication technologies, we’ve developed a thick vascularized tissue model to recapitulate physiologically relevant heterogeneous human alveoli. Specifically, the blood-air barrier of the alveolar model is simulated with two perfusable channels embedded in a thick vascularized tissue construct: a helical blood channel and a straight air channel. Spatially, the air channel is in the center and is surrounded by the blood channel. Human endothelial cells are seeded onto the inner surface of the blood channel and NCI-H23 cells (which carry a KRAS mutation) or untransformed alveolar epithelial cells derived from black subjects, are seeded on the inner surface of the air channel. The blood and air channels are perfused using cell medium and oxygenated air, respectively. The model is used for the study of potential LUAD therapeutic agents such as polyisoprenylated cysteinyl amide inhibitors (PCAIs), which target and disrupt the RAS-mediated signaling pathway. KRAS is the most commonly mutated oncogene in LUAD in blacks, and our experiments are aimed at ensuring that PCAIs are effective in black LUAD and may offer better treatment outcomes for ethnically/racially diverse patients in whom the RAS signaling pathway is frequently altered and for whom pharmaceutical therapy is necessitated by the late diagnoses. Citation Format: Nadine Belony, Bing Ren, Phuc Pham, Matthew Gregory, Pablo E. Puente, Nazarius S. Lamango, Ite A. Offringa, Yong Huang. Study of therapeutic effects of polyisoprenylated cysteinyl amide inhibitors on lung cancer cells of black patients using 3D-Printed alveolar model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4038.