1. Clinical and pathological predictors of engraftment for patient-derived xenografts in lung adenocarcinoma.
- Author
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Ogawa, Hiroyuki, Koga, Takamasa, Pham, Nhu-An, Bernards, Nicholas, Gregor, Alexander, Sata, Yuki, Kitazawa, Shinsuke, Hiraishi, Yoshihisa, Ishiwata, Tsukasa, Aragaki, Masato, Yokote, Fumi, Effat, Andrew, Kazlovich, Kate, Li, Quan, Hueniken, Katrina, Li, Ming, Maniwa, Yoshimasa, Tsao, Ming-Sound, and Yasufuku, Kazuhiro
- Subjects
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NUCLEOTIDE sequencing , *RAS oncogenes , *MOLECULAR pathology , *DRUG efficacy , *COMPUTED tomography - Abstract
• Patient-derived xenografts (PDXs) are important preclinical tool for cancer research as they preserve molecular, histological, and drug response features of patient tumors. • However, PDX establishment from patient tumor specimens is resource intensive and engraftment success rates for resectable lung adenocarcinoma (LUAD) is approximately 20 %. • Our analyses on the clinical, imaging, molecular and pathology features of 254 LUAD that were used to establish PDX models show that solid appearance of the tumors on preoperative CT images, solid predominant histology subtype, and KRAS or TP53 mutations were significantly associated with PDX growth in LUAD. • Our findings reveal a cost-effectiveness approach to enhance the success rates of LUAD PDX establishment. Patient-derived xenografts (PDXs) are increasingly utilized in preclinical drug efficacy studies due to their ability to retain the molecular, histological, and drug response characteristics of patient tumors. This study aimed to investigate the factors influencing the successful engraftment of PDXs. Lung adenocarcinoma PDXs were established using freshly resected tumor tissues obtained through surgery. Radiological data of pulmonary nodules from this PDX cohort were analyzed, categorizing them into solid tumors and tumors with ground-glass opacity (GGO) based on preoperative CT images. Gene mutation status was obtained from next generation sequencing data and MassARRAY panel. A total of 254 resected primary lung adenocarcinomas were utilized for PDX establishment, with successful initial engraftment in 58 cases (22.8 %); stable engraftment defined as at least three serial passages was observed in 43 cases (16.9 %). The stable engraftment rates of PDXs from solid tumors and tumors with GGO were 22.1 % (42 of 190 cases) and 1.6 % (1 of 64 cases), respectively (P < 0.001). Adenocarcinomas with advanced stage, poor differentiation, solid histologic subtype, and KRAS or TP53 gene mutations were associated with stable PDX engraftment. Avoiding tumors with GGO features could enhance the cost-effectiveness of establishing PDX models from early-stage resected lung adenocarcinomas. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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