2023 World Conference on Lung Cancer (Posters)-P1.07. Patient-Derived Xenografts from Thoracic Malignancies as Promising Preclinical Models

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Research conducted by the Department of Thoracic Surgery at Kumamoto University Hospital in Japan has demonstrated the potential of patient-derived xenografts (PDXs) from thoracic malignancies as valuable preclinical models for cancer research.<br /><br />Over a two-year period, the researchers successfully established 13 PDXs from 12 surgical lung cancer samples and one transbronchial biopsy sample. They found that the histology and molecular profiles of the PDXs closely matched those of the original patient tumors. Interestingly, drug sensitivity tests revealed varying responses among the PDXs, even within the same histological type, mirroring the heterogeneity seen in clinical patients.<br /><br />The PDXs were successfully passaged to more than the 5th generation, with major gene mutation information being maintained up to the 3rd generation. However, RNA-seq analysis showed that there were differences in biological changes among the PDXs, highlighting both inter-patient and intra-tumor heterogeneity.<br /><br />The researchers emphasized the importance of precision oncology, a clinical approach that takes into account the genetic and molecular profile of individual patients, and the need for appropriate preclinical models that can accurately recapitulate tumor heterogeneity. PDX models, created by engrafting patient tumors into immunodeficient mice, have the potential to meet this requirement.<br /><br />The study focused on thoracic malignancies with fewer patients and treatment options compared to more common forms of lung cancer. Tumor tissue obtained through surgical resection and biopsy was xenografted into immunodeficient mice for analysis. Drug therapies commonly used in clinical settings were also applied to the PDXs to generate resistant models and analyze biological changes.<br /><br />Overall, the researchers successfully developed a preclinical model that recapitulates tumor heterogeneity and closely mimics the tumor environment and drug sensitivity of clinical patients. The findings suggest that PDX models could be valuable tools for cancer diagnostics and therapeutics research. Further development and research in this area are needed to fully utilize the potential of PDX models in precision oncology.

Asset Subtitle

Kosuke Fujino

Meta Tag

Speaker Kosuke Fujino

Topic Tumor Biology: Translational Biology - Disease Modeling

Keywords

Department of Thoracic Surgery

Kumamoto University Hospital

Japan

patient-derived xenografts

PDXs

thoracic malignancies

preclinical models

cancer research

histology

molecular profiles