Abstract 2101: Patient-derived cells (PDCs) and organoids (PDOs) as critical platforms for developing next therapeutic strategies for NSCLC

Abstract Purpose: Patient-derived cells (PDCs) and organoids (PDOs) are constructed from pleural effusions to mimic the biological features of patients. In cancer research, PDC/PDOs could be a critical tool because they can recapitulate tumor mutations. Since commercial cell lines have difficulty mimicking the heterogeneity of tumors, PDC/PDOs are widely used for predicting the preclinical drug efficacy. The aim of this study is to show that the PDC/PDOs can be used as effective tools for developing new therapeutic strategy on non-small cell lung cancer (NSCLC). Experimental design: PDC/PDO models from malignant effusions were established as following. We succeeded the establishment with samples which are positive for malignancy in cytology tests and tumor colony formation. Mutations that cell harbors are confirmed by Sanger sequencing, Whole exome sequencing, or RNA-sequencing. Following the patient treatment history, we confirmed how does established patient derived model response to drugs that patient was treated. Results: A total of 54 PDCs and 171 PDOs were established from NSCLC patients, including models harboring EGFR mutations, KRAS mutations, uncommon EGFR mutations. 8 models of PDC and 7 models of PDO harbor various mutations of resistance mechanisms to EGFR-TKIs (T790M, C797S/C797G, MET amplification). Also, 4 models of PDC and PDO harbor uncommon EGFR mutations (EGFR G719S, L861Q, G719C/S768I, G719S/S768I) and 12 models of PDO harbors KRAS mutation. YUO-139 and YU-1092 are patient derived models that harbors uncommon EGFR mutation G719S and L861Q respectively. The models response to afatinib sensitively. IC50 of YUO-139 and YU-1092 to afatinib were 2.1 nM and 23.8 nM respectively. YUO-143 is a PDO model that harbors EGFR E19del/T790M/C797S which was derived from gefitinib and mavelertinib resistant patient revealed sensitivity to BLU-945 (IC50, 43 nM), a novel fourth-generation EGFR-TKI. Conclusions: Patient derived models could be a critical tool for developing therapeutic strategies for NSCLC. Citation Format: Sewon Park, Yunjoo Joo, Ju-hyeon Lee, Mi Ran Yun, Mi Ra Yu, Seung Yeon Oh, Eun Ji Lee, Dong Kwon Kim, Seul Lee, Kyumin Lim, Min Hee Hong, Sun Min Lim, Jii Bum Lee, Byoung Chul Cho. Patient-derived cells (PDCs) and organoids (PDOs) as critical platforms for developing next therapeutic strategies for NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2101.