Methodology of murine lung cancer mimics clinical lung adenocarcinoma progression and metastasis

TL;DR

This paper introduces a new mouse model that mimics human lung adenocarcinoma progression and metastasis for better cancer research.

Contribution

A novel methodology for creating immunogenic orthotopic lung adenocarcinoma mouse models with clinical relevance.

Findings

The model shows consistency in cancer initiation and metastasis across different cre virus concentrations.

Histological and immune profiles of the model align with clinical observations in lung adenocarcinoma.

Tumors in the model respond to clinical treatments, suggesting its utility for therapeutic testing.

Abstract

Lung cancer is the leading cause of cancer-related deaths, of which adenocarcinoma is the most common subtype. Despite this, lung adenocarcinoma and its metastasis are poorly understood, due to difficulties in feasibly recapitulating disease progression and predicting clinical benefits of therapy. We outline a methodology to develop immunogenic orthotopic lung adenocarcinoma mouse models, by injecting cell-specific cre viruses into the lung of a genetically engineered mouse, which mirrors cancer progression defined by the International Association for the Study of Lung Cancer. Evaluation of different cre virus/concentrations models demonstrate remarkable consistency in cancer initiation and metastasis, allowing for high throughput, while showing differences in timing and severity, offering greater flexibility when selecting models. Histological and immune profiles reflect clinical observations suggesting similar mechanisms are recapitulated and preliminary data show resultant tumors to be responsive to clinical treatments. We present a clinically relevant, next-generation murine model for studying lung adenocarcinoma.

The online version contains supplementary material available at 10.1038/s41598-025-90344-1.

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