Molecular links between COPD and lung cancer: new targets for drug discovery?
Gaetano CaramoriPaolo RuggeriSharon MumbyAntonio IeniFederica Lo BelloVrushali ChimankarChantal DonovanFilippo AndòFrancesco NuceraIrene CoppolinoGiovanni TuccariPhilip M HansbroIssssswan M AdcockPublished in: Expert opinion on therapeutic targets (2019)
COPD and lung cancer are leading causes of morbidity and mortality worldwide, and they share a common environmental risk factor in cigarette smoke exposure and a genetic predisposition represented by their incidence in only a fraction of smokers. This reflects the ability of cigarette smoke to induce an inflammatory response in the airways of susceptible smokers. Moreover, COPD could be a driving factor in lung cancer, by increasing oxidative stress and the resulting DNA damage and repression of the DNA repair mechanisms, chronic exposure to pro-inflammatory cytokines, repression of innate immunity and increased cellular proliferation. Areas covered: We have focused our review on the potential pathogenic molecular links between tobacco smoking-related COPD and lung cancer and the potential molecular targets for new drug development by understanding the common signaling pathways involved in COPD and lung cancer. Expert commentary: Research in this field is mostly limited to animal models or small clinical trials. Large clinical trials are needed but mostly combined models of COPD and lung cancer are necessary to investigate the processes caused by chronic inflammation, including genetic and epigenetic alteration, and the expression of inflammatory mediators that link COPD and lung cancer, to identify new molecular therapeutic targets.
Keyphrases
- chronic obstructive pulmonary disease
- oxidative stress
- lung function
- dna damage
- dna repair
- clinical trial
- inflammatory response
- drug discovery
- signaling pathway
- smoking cessation
- cystic fibrosis
- poor prognosis
- randomized controlled trial
- copy number
- long non coding rna
- climate change
- epithelial mesenchymal transition
- open label
- pi k akt
- toll like receptor
- phase iii
- double blind
- study protocol