Please use this identifier to cite or link to this item: http://hdl.handle.net/10400.16/2179
Title: Angiogenesis in NSCLC: is vessel co-option the trunk that sustains the branches?
Author: Coelho, A.
Gomes, M.
Catarino, R.
Rolfo, C.
Lopes, A.
Medeiros, R.
Araújo, A.
Keywords: NSCLC
angiogenesis
angiopoietin-2
anti-angiogenic strategies
vessel co-option
Issue Date: 13-Jun-2017
Publisher: Impact Journals
Citation: Oncotarget. 2017 Jun 13;8(24):39795-39804
Abstract: 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.
Peer review: yes
URI: http://hdl.handle.net/10400.16/2179
DOI: 10.18632/oncotarget.7794
ISSN: 1949-2553
Publisher Version: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=7794&pubmed-linkout=1
Appears in Collections:SOnc - Artigos publicados em revistas indexadas na Medline

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