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

Priyanka Sahu; Chantal Donovan; Keshav Raj Paudel; Sophie Pickles; Vrushali Chimankar; Richard Y Kim; Jay C Horvart; Kamal Dua; Antonio Ieni; Francesco Nucera; Helle Bielefeldt-Ohmann; Sarah Mazilli; Gaetano Caramori; J Guy Lyons; Philip M Hansbro

doi:10.3389/fonc.2023.1260411

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

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

Authors

Priyanka Sahu¹, Chantal Donovan^{1

2}, Keshav Raj Paudel³, Sophie Pickles³, Vrushali Chimankar³, Richard Y Kim^{1

2}, Jay C Horvart¹, Kamal Dua⁴, Antonio Ieni⁵, Francesco Nucera⁶, Helle Bielefeldt-Ohmann⁷, Sarah Mazilli⁸, Gaetano Caramori⁶, J Guy Lyons⁹, Philip M Hansbro^{1

3}

Affiliations

¹ Immune Health, Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
² University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW, Australia.
³ Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW, Australia.
⁴ Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW, Australia.
⁵ Department of Human Pathology in Adult and Developmental Age "Gaetano Barresi", Section of Anatomic Pathology, University of Messina, Messina, Italy.
⁶ Pneumologia, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF), Università degli Studi di Messina, Messina, Italy.
⁷ Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, QLD, Australia.
⁸ Department of Medicine, Boston University School of Medicine, Boston, MA, United States.
⁹ Department of Dermatology, The University of Sydney at Royal Prince Alfred Hospital, Sydney, Australia, and Centenary Institute, The University of Sydney, Sydney, NSW, Australia.

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.

Publication types

Review

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).