Abstract
Chronic obstructive pulmonary disease (COPD) patients are at increased risk of developing nonsmall cell lung carcinoma, irrespective of their smoking history. Although the mechanisms behind this observation are not clear, established drivers of carcinogenesis in COPD include oxidative stress and sustained chronic inflammation. Mitochondria are critical in these two processes and recent evidence links increased oxidative stress in COPD patients to mitochondrial damage. We therefore postulate that mitochondrial damage in COPD patients leads to increased oxidative stress and chronic inflammation, thereby increasing the risk of carcinogenesis.
The functional state of the mitochondrion is dependent on the balance between its biogenesis and degradation (mitophagy). Dysfunctional mitochondria are a source of oxidative stress and inflammasome activation. In COPD, there is impaired translocation of the ubiquitin-related degradation molecule Parkin following activation of the Pink1 mitophagy pathway, resulting in excessive dysfunctional mitochondria. We hypothesise that deranged pathways in mitochondrial biogenesis and mitophagy in COPD can account for the increased risk in carcinogenesis. To test this hypothesis, animal models exposed to cigarette smoke and developing emphysema and lung cancer should be developed. In the future, the use of mitochondria-based antioxidants should be studied as an adjunct with the aim of reducing the risk of COPD-associated cancer.
Abstract
We postulate that patients with COPD have increased risk of lung cancer as a result of mitochondrial dysfunction http://ow.ly/qzGv30fiAUm
Footnotes
Support statement: I.M. Adcock is supported by the Wellcome Trust (093080/Z/10/Z) and by the Dunhill Medical Trust (R368/0714). I.M. Adcock and K.F. Chung are supported by the Medical Research Council/Association of the British Pharmaceutical Industry (MRC/ABPI) COPDMAP consortium (G1001367/1). P.M. Hansbro is supported by grants from the Cancer Council NSW, the Australian Lung Foundation and the University of Newcastle (Australia), a National Health and Medical Research Council (Australia) Principal Research Fellowship and a Brawn Fellowship from the Faculty of Health and Medicine, University of Newcastle (Australia).
Conflict of interest: None declared.
Provenance: Submitted article, peer reviewed.
- Received April 2, 2017.
- Accepted July 17, 2017.
- Copyright ©ERS 2017.
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