Abstract
Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Although advances are being made towards earlier detection and the development of impactful targeted therapies and immunotherapies, the 5-year survival of patients with advanced disease is still below 20%. Effective cancer research relies on pre-clinical model systems that accurately reflect the evolutionary course of disease progression and mimic patient responses to therapy. Here, we review pre-clinical models, including genetically engineered mouse models and patient-derived materials, such as cell lines, primary cell cultures, explant cultures and xenografts, that are currently being used to interrogate NSCLC evolution from pre-invasive disease through locally invasive cancer to the metastatic colonization of distant organ sites.
Highlights
Lung cancer is the most commonly diagnosed cancer type globally for men and women, and constitutes almost one in five cancer deaths worldwide [1]
Lung cancers are classified as either small-cell lung cancer (SCLC; approx. 15%) or non-smallcell lung cancer (NSCLC; approx. 85%)
It is widely thought that lung adenocarcinoma (LUAD) develops from alveolar type II (AT2) epithelial cells or cells within bronchioalveolar duct junctions, whereas lung squamous cell carcinoma (LUSC) develops from basal epithelial cells in airways, data from animal models [3] and an increasing appreciation of the plasticity of lung epithelial cells [4] make this uncertain
Summary
Lung cancer is the most commonly diagnosed cancer type globally for men and women, and constitutes almost one in five cancer deaths worldwide [1]. LUAD typically arises in the distal lung, whereas LUSC arises centrally, probably reflecting different cells-of-origin for these two lung cancer types [2]. In NSCLC, independent of histological subtype, the standard first-line treatment for patients with stage I–III tumours is surgical resection, with adjuvant chemotherapy offering a small benefit for those with locally advanced stage III disease [10]. Along with enabling studies of early disease, these models allow us to compare the efficacy of novel therapies with established treatments and to study mechanisms of therapy resistance. Such systems have the potential to identify biomarkers of response for patient stratification and to inform future personalized therapies. We describe the progress that has been made to diversify the tools available for NSCLC research, discuss their relative advantages and disadvantages for particular research questions and reflect on some of the outstanding questions facing the field
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