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Review
. 2023 Sep 25:13:1260411.
doi: 10.3389/fonc.2023.1260411. eCollection 2023.

Pre-clinical lung squamous cell carcinoma mouse models to identify novel biomarkers and therapeutic interventions

Priyanka Sahu  1 , Chantal Donovan  1   2 , Keshav Raj Paudel  3 , Sophie Pickles  3 , Vrushali Chimankar  3 , Richard Y Kim  1   2 , Jay C Horvart  1 , Kamal Dua  4 , Antonio Ieni  5 , Francesco Nucera  6 , Helle Bielefeldt-Ohmann  7 , Sarah Mazilli  8 , Gaetano Caramori  6 , J Guy Lyons  9 , Philip M Hansbro  1   3
Affiliations
Review

Pre-clinical lung squamous cell carcinoma mouse models to identify novel biomarkers and therapeutic interventions

Priyanka Sahu et al. Front Oncol. .

Abstract

Primary lung carcinoma or lung cancer (LC) is classified into small-cell or non-small-cell (NSCLC) lung carcinoma. Lung squamous cell carcinoma (LSCC) is the second most common subtype of NSCLC responsible for 30% of all LCs, and its survival remains low with only 24% of patients living for five years or longer post-diagnosis primarily due to the advanced stage of tumors at the time of diagnosis. The pathogenesis of LSCC is still poorly understood and has hampered the development of effective diagnostics and therapies. This review highlights the known risk factors, genetic and epigenetic alterations, miRNA biomarkers linked to the development and diagnosis of LSCC and the lack of therapeutic strategies to target specifically LSCC. We will also discuss existing animal models of LSCC including carcinogen induced, transgenic and xenograft mouse models, and their advantages and limitations along with the chemopreventive studies and molecular studies conducted using them. The importance of developing new and improved mouse models will also be discussed that will provide further insights into the initiation and progression of LSCC, and enable the identification of new biomarkers and therapeutic targets.

Keywords: animal models; genetic and epigenetic alterations; lung cancer; risk factors; squamous cell carcinoma.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic diagram of the activity of cigarette smoke exposure in human lungs: Cigarette smoke (CS) consists of more than 60 tumour initiating carcinogens tested in both laboratory animal models and in humans. There are 20 potentially known carcinogens found in a burning cigarette which are involved in lung carcinogenesis. These include polycyclic aromatic hydrocarbons (PAH), N- nitrosamines, 1,3-butadiene and ethylene oxide, cadmium, and the radioactive compound 210PO. Few of these compound needs to be metabolically activated or undergoes decomposition to exert the carcinogenic effect. There are detoxifying enzymes such as cytochrome P450, glutathione S-transferase and UDP-glucuronosyl transferases which helps in removal of metabolically activated carcinogens. DNA adducts are formed during this process. When these adducts are left unrepaired by the DNA repair enzymes in the body, they result in genetic changes in key genes for cellular function. These altered genes, eventually leads to carcinogenesis.
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Grants and funding

PS is funded by University of Newcastle Postgraduate Research Scholarship (UNIPRS) and University of Newcastle Research Scholarship (UNRSE)/Lung Foundation Australia. CD is funded by a Fellowship and grant from the National Health and Medical Research Council (NHMRC) of Australia (1120152, 1138402). PMH is funded by a Fellowship and grants from the (NHMRC) of Australia (1079187, 1175134), The University of Technology Sydney, Lung Foundation of Australia and Cancer Council of NSW (1099119, 1157073), the International Association for the Study of Lung Cancer and the Maitland Cancer Appeal. KRP is funded by a fellowship from the International Association for the Study of Lung Cancer (IASLC).

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