Therapeutic approaches targeting molecular signaling pathways common to diabetes, lung diseases and cancer

Diabetes mellitus (DM), is the most common metabolic disease and is characterized by sustained hyper-glycemia. Accumulating evidences supports a strong association between DM and numerous lung dis-eases including chronic obstructive pulmonary disease (COPD), fibrosis, and lung cancer (LC). The global incidence of DM-associated lung disorders is rising and several ongoing studies, including clinical trials, aim to elucidate the molecular mechanisms linking DM with lung disorders, in particular LC. Several potential mechanisms, including hyperglycemia, hyperinsulinemia, glycation, inflammation, and hypoxia, are cited as plausible links between DM and LC. In addition, studies also propose a connec-tion between the use of anti-diabetic medications and reduction in the incidence of LC. However, the exact cause for DM associated lung diseases especially LC is not clear and is an area under intense inves-tigation. Herein, we review the biological links reported between DM and lung disorders with an empha-sis on LC. Furthermore, we report common signaling pathways (eg: TGF-B, IL-6, HIF-1, PDGF) and miRNAs that are dysregulated in DM and LC and serve as molecular targets for therapy. Finally, we propose a nanomedicine based approach for delivering therapeutics (eg: IL-24 plasmid DNA, HuR siRNA) to disrupt signaling pathways common to DM and LC and thus potentially treat DM-associated LC. Finally, we con-clude that the effective modulation of commonly regulated signaling pathways would help design novel therapeutic protocols for treating DM patients diagnosed with LC. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Diabetes mellitus (DM) is closely associated with lung diseases, particularly lung cancer (LC). Potential links include factors like hyperglycemia, hyperinsulinemia, and inflammation. Studies suggest that the use of anti-diabetic medications may reduce the incidence of lung cancer.