Tumor angiogenesis: causes, consequences, challenges and opportunities

Abstract

Tumor vascularization occurs through several distinct biological processes, which not only vary between tumor type and anatomic location, but also occur simultaneously within the same cancer tissue. These processes are orchestrated by a range of secreted factors and signaling pathways and can involve participation of non-endothelial cells, such as progenitors or cancer stem cells. Anti-angiogenic therapies using either antibodies or tyrosine kinase inhibitors have been approved to treat several types of cancer. However, the benefit of treatment has so far been modest, some patients not responding at all and others acquiring resistance. It is becoming increasingly clear that blocking tumors from accessing the circulation is not an easy task to accomplish. Tumor vessel functionality and gene expression often differ vastly when comparing different cancer subtypes, and vessel phenotype can be markedly heterogeneous within a single tumor. Here, we summarize the current understanding of cellular and molecular mechanisms involved in tumor angiogenesis and discuss challenges and opportunities associated with vascular targeting.

Antitumor Effect of a Novel Spiro-Acridine Compound is Associated with Up-Regulation of Th1-Type Responses and Antiangiogenic Action

“…The angiogenic process depending on the coordination of many factors is present in the tumor microenvironment and, therefore, understanding the interactions between these components is also relevant for therapeutic strategies against cancer [18,19]. Antiangiogenic therapy is an important target for antitumor drug action, since it prevents the emergence of new blood vessels that support tumor growth and induce metastasis [20]. Our data suggest that the AMTAC-17 mechanism of antitumor action involves an antiangiogenic effect, as previously reported for acridines [12].…”

Upregulation of lncRNA AGAP2‑AS1 is an independent predictor of poor survival in patients with clear cell renal carcinoma

“…Consistent with previous studies, the results of the current study demonstrated that increased AGAP2-AS1 expression was associated with poor overall survival and the potential mechanisms governing this may be the connection with stromal simulation (22,23), angiogenesis (24,25), epithelial-mesenchymal transition (26), hypoxia (27) or the notch signaling pathway (28,29). Angiogenesis, epithelial-mesenchymal transition and hypoxia are well-known hallmarks of cancers, and angiogenesis serves an important role in the progression of ccRCC via VEGF (30), FGF-2, PDGF, angiopoietins, ephrins, apelin (APLN) and chemokines (31,32). In the present study, the aberrant expression of AGAP2-AS1 was enriched in the process of angiogenesis, which may be activated by the PI3K/Akt pathway (33).…”

An Intricate Connection between Alternative Splicing and Phenotypic Plasticity in Development and Cancer

“…This process is triggered by paracrine signals [110] that stabilize HIF1α, the main activator of the angiogenic cascade. HIF1α accumulates in the cytoplasm and then translocates to the nucleus, promoting the transcription of genes with angiogenic potential such as VEGF, ANGPT1, and TIE2, platelet-derived growth factor (PDGF), PDGFR receptor, fibroblast growth factor (FGF), FGFR receptor, NOTCH1, and its ligand DLL4 [111].…”