Lung cancer still represents the leading cause of cancer-related death, globally. Likewise, malnutrition and inactivity represent a major risk for loss of functional pulmonary capacities influencing overall lung cancer severity. Therefore, the adhesion to an appropriate health lifestyle is crucial in the management of lung cancer patients despite the subtype of cancer. This review aims to summarize the available knowledge about dietary approaches as well as physical activity as the major factors that decrease the risk towards lung cancer, and improve the response to therapies. We discuss the most significant dietary schemes positively associated to body composition and prognosis of lung cancer and the main molecular processes regulated by specific diet schemes, functional foods and physical activity, i.e., inflammation and oxidative stress. Finally, we report evidence demonstrating that dysbiosis of lung and/or gut microbiome, as well as their interconnection (the gut–lung axis), are strictly related to dietary patterns and regular physical activity playing a key role in lung cancer formation and progression, opening to the avenue of modulating the microbiome as coadjuvant therapy. Altogether, the evidence reported in this review highlights the necessity to consider non-pharmacological interventions (nutrition and physical activity) as effective adjunctive strategies in the management of lung cancer.

Adiponectin and leptin are two abundant adipokines with different properties but both described such as potent factors regulating angiogenesis. AdipoRon is a small-molecule that, binding to AdipoRs receptors, acts as an adiponectin agonist. Here, we investigated the effects of AdipoRon and leptin on viability, migration and tube formation on a human in vitro model, the human umbilical vein endothelial cells (HUVEC) focusing on the expression of the main endothelial angiogenic factors: hypoxia-inducible factor 1-alpha (HIF-1α), C-X-C motif chemokine ligand 1 (CXCL1), vascular endothelial growth factor A (VEGF-A), matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9). Treatments with VEGF-A were used as positive control. Our data revealed that, at 24 h treatment, proliferation of HUVEC endothelial cells was not influenced by AdipoRon or leptin administration; after 48 h longer exposure time, the viability was negatively influenced by AdipoRon while leptin treatment and the combination of AdipoRon+leptin produced no effects. In addition, AdipoRon induced a significant increase in complete tubular structures together with induction of cell migration while, on the contrary, leptin did not induce tube formation and inhibited cell migration; interestingly, the co-treatment with both AdipoRon and leptin determined a significant decrease of the tubular structures and cell migration indicating that leptin antagonizes AdipoRon effects. Finally, we found that the effects induced by AdipoRon administration are accompanied by an increase in the expression of CXCL1, VEGF-A, MMP-2 and MMP-9. In conclusion, our data sustain the active role of adiponectin and leptin in linking adipose tissue with the vascular endothelium encouraging the further deepening of the role of adipokines in new vessel’s formation, to candidate them as therapeutic targets.