Browsing by Author "Rolfo, C."
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- Angiogenesis in NSCLC: is vessel co-option the trunk that sustains the branches?Publication . Coelho, A.; Gomes, M.; Catarino, R.; Rolfo, C.; Lopes, A.; Medeiros, R.; Araújo, A.The critical role of angiogenesis in tumor development makes its inhibition a valuable new approach in therapy, rapidly making anti-angiogenesis a major focus in research. While the VEGF/VEGFR pathway is the main target of the approved anti-angiogenic molecules in NSCLC treatment, the results obtained are still modest, especially due to resistance mechanisms. Accumulating scientific data show that vessel co-option is an alternative mechanism to angiogenesis during tumor development in well-vascularized organs such as the lungs, where tumor cells highjack the existing vasculature to obtain its blood supply in a non-angiogenic fashion. This can explain the low/lack of response to current anti-angiogenic strategies. The same principle applies to lung metastases of other primary tumors. The exact mechanisms of vessel co-option need to be further elucidated, but it is known that the co-opted vessels regress by the action of Angiopoietin-2 (Ang-2), a vessel destabilizing cytokine expressed by the endothelial cells of the pre-existing mature vessels. In the absence of VEGF, vessel regression leads to tumor cell loss and hypoxia, with a subsequent switch to a neoangiogenic phenotype by the remaining tumor cells. Unravelling the vessel co-option mechanisms and involved players may be fruitful for numerous reasons, and the particularities of this form of vascularization should be carefully considered when planning anti-angiogenic interventions or designing clinical trials for this purpose. In view of the current knowledge, rationale for therapeutic approaches of dual inhibition of Ang-2 and VEGF are swiftly gaining strength and may serve as a launchpad to more successful NSCLC anti-vascular treatments.
- Exosomes genetic cargo in lung cancer: a truly Pandora's boxPublication . Reclusa, P.; Sirera, R.; Araujo, A.; Giallombardo, M.; Valentino, A.; Sorber, L.; Bazo, I.; Pauwels, P.; Rolfo, C.Lung cancer is a highly lethal disease. Targeted therapies have been developed in last years, however survival rates are not improving due to the delay in the diagnosis, making biomarkers one of the most interesting fields of study in cancer. Liquid biopsy has raised as an alternative to tissue biopsy due to improvements in analytical techniques for circulating tumor cells (CTCs), cell free DNA and exosomes. Among all, exosomes have raised as one of the most promising tools to understand the tumor due to their stability in the blood and their similarity to the cells of origin. In the last years, different alterations have been described inside the exosomes derived from non-small cell lung cancer (NSCLC) cells mirroring the processes inside these tumoral cells, such as EGFR mutation, translocations or microRNA (miRNA) deregulation. All these studies have opened the window to a new world of possibilities in the study of tumor biomarkers.
- Exosomes isolation and characterization in serum is feasible in non-small cell lung cancer patients: critical analysis of evidence and potential role in clinical practicePublication . Taverna, S.; Giallombardo, M.; Gil-Bazo, I.; Carreca, A.; Castiglia, M.; Chacártegui, J.; Araujo, A.; Alessandro, R.; Pauwels, P.; Peeters, M.; Rolfo, C.Exosomes are nano-sized vesicles of endolysosomal origin, released by several cytotypes in physiological and pathological conditions. Tumor derived exosomes, interacting with other cells of the tumor microenvironment, modulate tumor progression, angiogenic switch, metastasis, and immune escape. Recently, extracellular vesicles were proposed as excellent biomarkers for disease monitoring and prognosis in cancer patients. Non-small cell lung cancer (NSCLC) has a poor 5-year survival rate due to the delay in the detection of the disease. The majority of patients are diagnosed in an advanced disease stage. Exosomes might be promising beneficial tools as biomarker candidates in the scenario of NSCLC, since they contain both, proteins and miRNAs. The clinical case reported in this manuscript is a proof of concept revealing that NSCLC exosomes and sorted miRNAs might constitute, in a near future, novel biomarkers. This review summarizes the role of exosomes in NSCLC, focusing on the importance of exosomal microRNAs in lung cancer diagnosis and prognosis.