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Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

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Abstract

Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship.

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Acknowledgements

SSS is supported by the Clifford Craig Foundation Launceston, Thoracic Society of Australia and New Zealand (TSANZ) and Boehringer Ingelheim COPD Research Award; PMH is supported by an NHMRC Principal Research Fellowship and a Brawn Fellowship, Faculty of Health, University of Newcastle; VC is supported by a Cancer Council WA postdoctoral fellowship; MKJ is supported by a training fellowship from the Gulf Coast Consortia, on the Computational Cancer Biology Training Program; and PS is supported by the Rebecca L. Cooper Medical Research Foundation, Australia, and the Chancellors Fellowship Programme, University of Technology Sydney (UTS).

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Mathew Suji Eapen, Anna-Karin Larsson‑Callerfelt, Mohit K. Jolly, Stephen Myers, Pawan Sharma, Bernadette Jones, Md Atiqur Rahman, James Markos, Collin Chia, Josie Larby, Greg Haug, Ashutosh Hardikar, Heinrich C. Weber, George Mabeza and Vinicius Cavalheri declare no conflicts of interest. Sukhwinder Singh Sohal reports grants from the Thoracic Society of Australia and New Zealand (TSANZ), Boehringer Ingelheim and the Clifford Craig Foundation. Philip M. Hansbro has no conflicts of interest related to this manuscript, aside from the fact that this article relates to mouse models of lung cancer and COPD, which we regularly use. Yet H. Khor reports grants from the National Health and Medical Research Council and Boehringer Ingelheim, and non-financial support from Air Liquide, as well as honorarium from Boehringer Ingelheim, Roche and Astra Zeneca, outside the submitted work. Christine F. McDonald has received speakers fees from, and participated in advisory boards for, GSK, Pfizer and Novartis, and has donated speaker fees from Menarini to her hospital.

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Eapen, M.S., Hansbro, P.M., Larsson‑Callerfelt, AK. et al. Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities. Drugs 78, 1717–1740 (2018). https://doi.org/10.1007/s40265-018-1001-8

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