Molecular Characteristics of Patient-Derived Tumor Xenografts: Similarities to Patient Tumors and Relevance for Biomarker Discovery

Vuaroqueaux, Vincent; Peille, Anne-Lise; Zeitouni, Bruno; Eades‐Perner, Anne‐Marie; Fiebig, Heinz‐Herbert

doi:10.1007/978-3-319-57424-0_17

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“…Over the last decade, propagation of patient tumors in PDX is increasingly being used as a model system in anti-cancer drug discovery and development as well as for biomarker investigation 22,23 . It is therefore important to understand the intra-tumor and inter-tumor heterogeneity that exists in both the parental tumors and the established PDX models, so that PDX models can be optimally utilized.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of molecular subtypes and clonal selection during establishment of patient-derived tumor xenografts from gastric adenocarcinoma

et al. 2020

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Patient-derived xenografts (PDX) have emerged as an important translational research tool for understanding tumor biology and enabling drug efficacy testing. They are established by transfer of patient tumor into immune compromised mice with the intent of using them as Avatars; operating under the assumption that they closely resemble patient tumors. In this study, we established 27 PDX from 100 resected gastric cancers and studied their fidelity in histological and molecular subtypes. We show that the established PDX preserved histology and molecular subtypes of parental tumors. However, in depth investigation of the entire cohort revealed that not all histological and molecular subtypes are established. Also, for the established PDX models, genetic changes are selected at early passages and rare subclones can emerge in PDX. This study highlights the importance of considering the molecular and evolutionary characteristics of PDX for a proper use of such models, particularly for Avatar trials.

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Section: Discussionmentioning

confidence: 99%