PT  - JOURNAL ARTICLE
AU  - Francois Ng Kee Kwong
AU  - Andrew G. Nicholson
AU  - Celeste L. Harrison
AU  - Philip M. Hansbro
AU  - Ian M. Adcock
AU  - Kian Fan Chung
TI  - Is mitochondrial dysfunction a driving mechanism linking COPD to nonsmall cell lung carcinoma?
AID  - 10.1183/16000617.0040-2017
DP  - 2017 Dec 31
TA  - European Respiratory Review
PG  - 170040
VI  - 26
IP  - 146
4099  - http://err.ersjournals.com/content/26/146/170040.short
4100  - http://err.ersjournals.com/content/26/146/170040.full
SO  - EUROPEAN RESPIRATORY REVIEW2017 Dec 31; 26
AB  - 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.We postulate that patients with COPD have increased risk of lung cancer as a result of mitochondrial dysfunction http://ow.ly/qzGv30fiAUm