Document Type

Article

Publication Date

11-15-2022

Publication Title

Cancer research

Keywords

JMG, JGM, JCA, Humans, Animals, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Heterografts, Xenograft Model Antitumor Assays, Adenocarcinoma of Lung, Disease Models, Animal

JAX Source

Cancer Res. 2022;82(22):4126-38

Volume

82

Issue

22

First Page

4126

Last Page

4138

ISSN

1538-7445

PMID

36069866

DOI

https://doi.org/10.1158/0008-5472.CAN-22-0948

Grant

P30 CA034196 (to E.T. Liu), P30 CA093373 (to P.N. Lara), SU2C 201502309 (to D.R. Gandara), 5U01 CA180944 (to E.T. Liu), R01 CA089713 (to C.J. Bult). The Jackson Laboratory Director’s Innovation Fund (to C.J. Bult and S.D. Airhart), the Maine Cancer Foundation (to C.J. Bult), the Kleeberg Foun- dation (to C.J. Bult), and the Hope Foundation (to E.T. Liu).

Abstract

UNLABELLED: Patient-derived xenograft (PDX) models are an effective preclinical in vivo platform for testing the efficacy of novel drugs and drug combinations for cancer therapeutics. Here we describe a repository of 79 genomically and clinically annotated lung cancer PDXs available from The Jackson Laboratory that have been extensively characterized for histopathologic features, mutational profiles, gene expression, and copy-number aberrations. Most of the PDXs are models of non-small cell lung cancer (NSCLC), including 37 lung adenocarcinoma (LUAD) and 33 lung squamous cell carcinoma (LUSC) models. Other lung cancer models in the repository include four small cell carcinomas, two large cell neuroendocrine carcinomas, two adenosquamous carcinomas, and one pleomorphic carcinoma. Models with both de novo and acquired resistance to targeted therapies with tyrosine kinase inhibitors are available in the collection. The genomic profiles of the LUAD and LUSC PDX models are consistent with those observed in patient tumors from The Cancer Genome Atlas and previously characterized gene expression-based molecular subtypes. Clinically relevant mutations identified in the original patient tumors were confirmed in engrafted PDX tumors. Treatment studies performed in a subset of the models recapitulated the responses expected on the basis of the observed genomic profiles. These models therefore serve as a valuable preclinical platform for translational cancer research.

SIGNIFICANCE: Patient-derived xenografts of lung cancer retain key features observed in the originating patient tumors and show expected responses to treatment with standard-of-care agents, providing experimentally tractable and reproducible models for preclinical investigations.

Comments

This open access article is distributed under the Creative Commons Attribution- NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.

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