American Association for Cancer Research
10780432ccr141589-sup-133590_1_supp_data_2727046_n22jsq.docx (39.12 kB)

Supplementary table S3 from Patient-Derived Xenografts from Non–Small Cell Lung Cancer Brain Metastases Are Valuable Translational Platforms for the Development of Personalized Targeted Therapy

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posted on 2023-03-31, 19:06 authored by Hye Won Lee, Jung-il Lee, Se Jeong Lee, Hyun Jung Cho, Hye Jin Song, Da Eun Jeong, Yun Jee Seo, Sang Shin, Je-Gun Joung, Yong-Jun Kwon, Yoon-La Choi, Woong-Yang Park, Hyun Moo Lee, Ho Jun Seol, Young Mog Shim, Kyeung Min Joo, Do-Hyun Nam

Supplementary table S3. Clinicopathological characteristics and in vivo tumorigenicity of primary NSCLC cases.



Purpose: The increasing prevalence of distant metastases from non–small cell lung cancer (NSCLC) indicates an urgent need for novel therapeutic modalities. Brain metastasis is particularly common in NSCLC, with severe adverse effects on clinical prognosis. Although the molecular heterogeneity of NSCLC and availability of various targeted agents suggest personalized therapeutic approaches for such brain metastases, further development of appropriate preclinical models is needed to validate the strategies.Experimental Design: We established patient-derived xenografts (PDX) using NSCLC brain metastasis surgical samples and elucidated their possible preclinical and clinical implications for personalized treatment.Results: NSCLC brain metastases (n = 34) showed a significantly higher successful PDX establishment rate than primary specimens (n = 64; 74% vs. 23%). PDXs derived from NSCLC brain metastases recapitulated the pathologic, genetic, and functional properties of corresponding parental tumors. Furthermore, tumor spheres established in vitro from the xenografts under serum-free conditions maintained their in vivo brain metastatic potential. Differential phenotypic and molecular responses to 20 targeted agents could subsequently be screened in vitro using these NSCLC PDXs derived from brain metastases. Although PDX establishment from primary NSCLCs was significantly influenced by histologic subtype, clinical aggressiveness, and genetic alteration status, the brain metastases exhibited consistently adequate in vivo tumor take rate and in vitro tumor sphere formation capacity, regardless of clinical and molecular conditions.Conclusions: Therefore, PDXs from NSCLC brain metastases may better represent the heterogeneous advanced NSCLC population and could be utilized as preclinical models to meet unmet clinical needs such as drug screening for personalized treatments. Clin Cancer Res; 21(5); 1172–82. ©2014 AACR.

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