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Review
. 2021 Jan;11(1):200247.
doi: 10.1098/rsob.200247. Epub 2021 Jan 13.

Progress towards non-small-cell lung cancer models that represent clinical evolutionary trajectories

Robert E Hynds  1   2 , Kristopher K Frese  3   4 , David R Pearce  1 , Eva Grönroos  2 , Caroline Dive  3   4 , Charles Swanton  1   2
Affiliations
Review

Progress towards non-small-cell lung cancer models that represent clinical evolutionary trajectories

Robert E Hynds et al. Open Biol. 2021 Jan.

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.

Keywords: cancer evolution; cell lines; genetically engineered mouse models; model systems; organoids; patient-derived xenografts.

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Conflict of interest statement

C.S. acknowledges grant support from Pfizer, AstraZeneca, Bristol Myers Squibb, Roche-Ventana, Boehringer-Ingelheim, Archer Dx Inc (collaboration in minimal residual disease sequencing technologies) and Ono Pharmaceutical, is an AstraZeneca Advisory Board member and Chief Investigator for the MeRmaiD1 clinical trial, has consulted for Pfizer, Novartis, GlaxoSmithKline, MSD, Bristol Myers Squibb, Celgene, AstraZeneca, Illumina, Genentech, Roche-Ventana, GRAIL, Medicxi, Bicycle Therapeutics and the Sarah Cannon Research Institute, has stock options in Apogen Biotechnologies, Epic Bioscience and GRAIL, and has stock options and is co-founder of Achilles Therapeutics. C.S. holds European patents relating to assay technology to detect tumour recurrence (PCT/GB2017/053289), targeting neoantigens (PCT/EP2016/059401), identifying patent response to immune checkpoint blockade (PCT/EP2016/071471), determining HLA LOH (PCT/GB2018/052004), predicting survival rates of patients with cancer (PCT/GB2020/050221) and identifying patients who respond to cancer treatment (PCT/GB2018/051912), a US patent relating to detecting tumour mutations (PCT/US2017/28013), and both a European and US patent related to identifying insertion/deletion mutation targets (PCT/GB2018/051892). C.D. acknowledges research funding/grants received from AstraZeneca, Astex Pharmaceuticals, Bioven, Amgen, Carrick Therapeutics, Merck AG, Taiho Oncology, GSK, Bayer, Boehringer Ingelheim, Roche, BMS, Novartis, Celgene, Epigene Therapeutics Inc., Angle PLC, Menarini and Clearbridge Biomedics. C.D. has received honoraria for consultancy/advisory board from Biocartis, Merck, AstraZeneca and Illumina.

Figures

Figure 1.
Figure 1.
A timeline of advances in pre-clinical models of non-small-cell lung cancer. Created with BioRender.com based on [–28].
Figure 2.
Figure 2.
Pre-clinical models across the disease course of non-small-cell lung cancer. Created with BioRender.com.
See this image and copyright information in PMC

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