Background and rationale. The therapeutic interventions against lung cancer are currently based on a fully personalized approach to the disease with considerable improvement of patients’ outcome. Alongside continuous scientific progresses and research investments, massive technologic efforts, innovative challenges, and consolidated achievements together with research investments are at the bases of the engineering and manufacturing revolution that allows a significant gain in clinical setting. Aim and methods. The scope of this review is thus to focus, rather than on the biologic traits, on the analysis of the precision sensors and novel generation materials, as semiconductors, which are below the clinical development of personalized diagnosis and treatment. In this perspective, a careful revision and analysis of the state of the art of the literature and experimental knowledge is presented. Results. Novel materials are being used in the development of personalized diagnosis and treatment for lung cancer. Among them, semiconductors are used to analyze volatile cancer compounds and allow early disease diagnosis. Moreover, they can be used to generate MEMS which have found an application in advanced imaging techniques as well as in drug delivery devices. Conclusions. Overall, these issues represent critical issues only partially known and generally underestimated by the clinical community. These novel micro-technology-based biosensing devices, based on the use of molecules at atomic concentrations, are crucial for clinical innovation since they have allowed the recent significant advances in cancer biology deciphering as well as in disease detection and therapy. There is an urgent need to create a stronger dialogue between technologists, basic researchers, and clinicians to address all scientific and manufacturing efforts towards a real improvement in patients’ outcome. Here, great attention is focused on their application against lung cancer, from their exploitations in translational research to their application in diagnosis and treatment development, to ensure early diagnosis and better clinical outcomes.

The efficacy of pre-emptive therapy in the prevention of cytomegalovirus (CMV) disease and the potential association of CMV infection with the occurrence of chronic lung allograft dysfunction (CLAD) was evaluated in 129 lung transplant recipients receiving pre-emptive therapy based on pp65-antigenemia or CMV-DNA in the blood and in the bronchoalveolar lavage. Seventy-one (55%) patients received pre-emptive ganciclovir/valganciclovir (GCV/VGCV) for CMV infection for a median of 28 (9–191) days. Possible CMV disease occurred in six (5%) patients and was healed after the GCV/VGCV therapy. The cumulative incidence of CLAD was 38% and 54% at 5 and 10 years. Acute rejection and CMV load in the blood (but not in the lung) were independent predictors of the occurrence of CLAD. Pre-emptive therapy is highly effective in preventing CMV disease in lung recipients and does not induce a superior incidence of CLAD compared to what reported for other cohorts of patients who received an extended antiviral prophylaxis.

Recent studies have emphasized the critical role of alteration in cellular plasticity in the development of fibrotic disorders, particularly pulmonary fibrosis, prompting further investigation into molecular mechanisms and therapeutic approaches. In this context, Precision Cut Lung Slices (PCLSs) emerge as a valuable ex vivo research tool. The process of PCLSs generation preserves most features of the naïve lung tissue, such as its architecture and complex cellular composition. We previously stimulated normal lung PCLSs with two different stimuli (fibrotic cocktail, composed by platelet lysate and TGFβ, or neutrophil extracellular traps) and we observed a significant elevation of Epithelial–Mesenchymal Transition (EMT) markers from 24 h to 72 h of culture. The aim of our work was to exploit this PCLSs based ex vivo model of EMT, to evaluate the effect of imatinib, an old tyrosine kinase inhibitor with reported anti-remodeling activities in vitro and in animal models. Imatinib treatment significantly decreased α-SMA and collagen expression already starting from 24 h on stimulated PCLS. Imatinib showed a significant toxicity on unstimulated cells (3-fold increase in ACTA2 expression levels at 24 h, 1.5-fold increase in COL1A1 expression levels at 24 h, 2-fold increase in COL3A1 expression levels at 72 h). Further evaluations on specific cell lines pointed out that drug effects were mainly directed towards A549 and LFs. In conclusion, our model confirms the anti-remodeling activity of imatinib but suggests that its direct delivery to alveolar epithelial cells as recently attempted by inhalatory preparation of the drug might be associated with a non-negligible epithelial cell toxicity.

Among interstitial lung diseases, idiopathic pulmonary fibrosis (IPF) represents a condition rapidly progressive to respiratory failure and patients’s death. Notably, the incidence of lung cancer (LC) in patients already affected by IPF is significantly higher than in general population. Moreover these cases are often neglected and deprived of active oncologic treatments. We here aim at identifying ILD variables predictive of patient outcome by analysing present exhaustive data from 42 patients featuring LC and co-existing IPF. The entire dataset was then analysed by using the JMP partition algorithm which is able to search all possible splits of best response predictors and variable associated to outcome (survival). The row overall survival curve showed differences based on patients’ gender, being women survival lower than men’ one (Fig 1, a). The distribution of probabilities of the value “survival” has been to the five groups, representing the different first line therapeutic strategy. This analysis allows to point out that highest probability of survival occurs in the sub-population who underwent surgery against cancer. (Fig. 1, panel B-C). The co-existence of previous diagnosis of COPD and the absence of circulating autoantibodies act as protective factors being associated with higher survival probability (Fig. 2). Quite unexpectedly this approach showed that IPF related features as well as respiratory performance are associated to patients’ outcome (prediction) irrespective of those associated with the concomitant tumor (histology and stage).

Background: Allogenic bone marrow derived mesenchimal stromal cells (Allo-BM MSCs) represent a promising therapy for chronic lung allograft dysfunction (CLAD) after lung transplantation, due to their immunomodulatory and tolerogenic properties, as shown in preclinical and clinical models and small monocentric case series(Chambers DC et al, doi: 10.1002/sctm.16-0372). Methods: Five patients with advanced CLAD and progressive functional deterioration, which experienced all possible treatment lines, underwent monthly infusion of allo-BM MSCs ( 106cells per kilogram) as salvage treatment. Beside recording clinical follow up and lung function, we analysed serum levels of miR-21 and IL-4,IL2,IP-10,IL-1beta, TNF-alpha, MCP-1,IL-17 A, IL-6,IL-10,IFN-gamma, il-12p70 and IL8 at 0-6 months treatment. Results:: After initiation of therapy with MSCs, FEV1 stabilized in 4 patients and slowered decline in 1 patient (graph 1). No adverse effects attributable to MSCs therapy, no increase in the frequency of infections and no significant change in cytokines and miR levels were detected. Conclusion: Monthly intravenous treatment with low dose of Allo-BM MSCs is well tolerated, and functional results on a small cohort of patients suggest that might stabilize graft function even in lung recipients with advanced CLAD.