Lung cancer being the most prevalent malignancy in men and the 3rd most frequent in women is still associated with dismal prognosis due to advanced disease at the time of diagnosis. Novel targeted therapies are already on the market and several others are under investigation. However non-specific cytotoxic agents still remain the cornerstone of treatment for many patients. Central airways stenosis or obstruction may often complicate and decrease quality of life and survival of these patients. Interventional pulmonology modalities (mainly debulking and stent placement) can alleviate symptoms related to airways stenosis and improve the quality of life of patients. Mitomycin C and sirolimus have been observed to assist a successful stent placement by reducing granuloma tissue formation. Additionally, these drugs enhance the normal tissue ability against cancer cell infiltration. In this mini review we will concentrate on mitomycin C and sirolimus and their use in stent placement.

Background: EBUS guided trans-bronchial biopsy became routine in diagnosis of peripheral pulmonary lesions (PPL). Suction catheter-biopsy is a technique for obtaining a tissue sample from peripheral lung parenchyma. Aim of this study was to evaluate diagnostic efficiency, feasibility and safety of EBUS guided suction catheter-biopsy (SCB) in comparison to trans-bronchial biopsy (TBB) in diagnosis of PPL. The main intention was to demonstrate non-inferiority of the technique over trans-bronchial biopsy, especially when used under navigation of the EBUS.Methods: Radial EBUS probe (UM-3R, Olympus Co, Japan.) without guiding sheath was used to navigate suction catheter and TBB forceps to the PPL. The catheter was connected to the collection canister via vacuum pump. The SCB specimens were fixed with 10% buffered formalin.Results: There were 168 patients enrolled in this study; 69.9% males and 30.1% females. Main lesion diameter was 4.1±1.9 cm. Majority of patients, 131(77.9%) were diagnosed with lung cancer. Per-biopsy calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for EBUS-SCB were 92.4%, 100%, 100% and 67.7%, respectively. Corresponding values for EBUS-TBB were 92.3%, 100%, 100% and 69.7%. Only the size of the lesion significantly influenced (p=0.005) diagnostic performance. Complications occurred in 2 patients; one pneumothorax and one excessive bleeding.Conclusion: EBUS guided SCB is efficient, feasible and safe in diagnosis of peripheral lung cancer. The technique is complementary to trans-bronchial biopsy.

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Intratumoral heterogeneity in lung cancer is essential for evasion of immune surveillance by tumor cells and establishment of immunosuppression. Gathering data reveal that circular RNAs (circRNAs), play a role in the pathogenesis and progression of lung cancer. Particularly Kras-driven circRNA signaling triggers infiltration of myeloid-associated tumor macrophages in lung tumor microenvironment thus establishing immune deregulation, and immunosuppression but the exact pathogenic mechanism is still unknown. In this study, we investigate the role of oncogenic Kras signaling in circRNA-related immunosuppression and its involvement in tumoral chemoresistance. The expression pattern of circRNAs HIPK3 and PTK2 was determined using quantitative polymerase chain reaction (qPCR) in lung cancer patient samples and cell lines. Apoptosis was analyzed by Annexin V/PI staining and FACS detection. M2 macrophage polarization and MDSC subset analysis (Gr1−/CD11b−, Gr1−/CD11b+) were determined by flow cytometry. Tumor growth and metastatic potential were determined in vivo in C57BL/6 mice. Findings reveal intra-epithelial CD163+/CD206+ M2 macrophages to drive Kras immunosuppressive chemoresistance through myeloid differentiation. In particular, monocytic MDSC subsets Gr1−/CD11b−, Gr1−/CD11b+ triggered an M2-dependent immune response, creating an immunosuppressive tumor-promoting network via circHIPK3/PTK2 enrichment. Specifically, upregulation of exosomal cicHIPK3/PTK2 expression prompted Kras-driven intratumoral heterogeneity and guided lymph node metastasis in C57BL/6 mice. Consequent co-inhibition of circPTK2/M2 macrophage signaling suppressed lung tumor growth along with metastatic potential and prolonged survival in vivo. Taken together, these results demonstrate the key role of myeloid-associated macrophages in sustaining lung immunosuppressive neoplasia through circRNA regulation and represent a potential therapeutic target for clinical intervention in metastatic lung cancer.