Establishment of a non-small-cell lung cancer-liver metastasis patient-derived tumor xenograft model for the evaluation of patient-tailored chemotherapy.

Xue Yang,Gaopei Meng

doi:10.1042/bsr20182082

Abstract

In order to optimize patient-tailored chemotherapy, a non-small-cell lung cancer (NSCLC)-liver metastasis patient-derived tumor xenograft (PDTX) model is developed. Computed tomography (CT)-guided NSCLC percutaneous biopsy was subcutaneously inoculated into the flank of non-obese diabetic/severe combined immunodeficiency (NOD/SCID) female mice (PDTX F1) and allowed to reach 500 mm3 volume. Then, the tumors were re-transplanted into Balb/c nude mice and liver metastasis was confirmed (PDTX F2), which were further assigned into doxorubicin (DOX), docetaxel (DTX), and non-treatment control group. H&E staining and Keratin 20 (CK20) staining were applied to determine the consistency of PDTX models and primary tumors. Tumor growth curve, body weight, and the expression of p65 nuclear factor (NF)-κB and the secretion of interferon (IFN)-γ were investigated. The successive transplant procedure can induce the NSCLC-liver metastasis PDTX model, and morphological and structural characteristics of PDTX models (F2) were in accordance with primary tumors. DOX and DTX could delay tumor growth, activate the NF-κB pathway, and promote IFN-γ secretion in the PDTX models. The NSCLC-liver metastasis PDTX model is established and provides a powerful mean to assess chemotherapeutic efficacy.

Highlights

As one of the most common cancers worldwide, approximately 30–40% non-small-cell lung cancer (NSCLC) patients following the first diagnosis will present with distant metastases, such as liver, brain, lymph node, bone, and adrenal gland [1,2]
The passaged Patient-derived tumor xenograft (PDTX) models are biologically stable in terms of tumor architecture, mutational status, global gene-expression patterns, drug responsiveness, and metastatic potential, which can be utilized as an information-rich preclinical resource for predictive biomarker discovery and drug activity screen
Three NSCLC patients accompanied with liver metastasis were recruited, and only one PDTX model derived from one patient was established

Summary

Introduction

As one of the most common cancers worldwide, approximately 30–40% non-small-cell lung cancer (NSCLC) patients following the first diagnosis will present with distant metastases, such as liver, brain, lymph node, bone, and adrenal gland [1,2]. Treatments of liver metastases from NSCLC consist only of systemic therapy using cytotoxic (doxorubicin (DOX) and docetaxel (DTX)), molecularly targeted agents (EGFR mutations, ALK rearrangements, and ROS1 rearrangements target), palliative radiotherapy, and immunotherapy. In some cases, these medications may result in long-term control of liver metastases from NSCLC [6,7]. The passaged PDTX models are biologically stable in terms of tumor architecture, mutational status, global gene-expression patterns, drug responsiveness, and metastatic potential, which can be utilized as an information-rich preclinical resource for predictive biomarker discovery and drug activity screen

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