Abstract |
In contrast to mechanisms taking place during resistance to chemotherapies or other targeted therapies, compensatory adaptation to angiogenesis blockade does not imply a mutational alteration of genes encoding drug targets or multidrug resistance mechanisms but instead involves intrinsic or acquired activation of compensatory angiogenic pathways. In this article we highlight hypoxia-regulated and immune-mediated mechanisms that converge in endothelial cell programs and preserve angiogenesis in settings of vascular endothelial growth factor ( VEGF) blockade. These mechanisms involve mobilization of myeloid cell populations and activation of cytokine- and chemokine-driven circuits operating during intrinsic and acquired resistance to anti-angiogenic therapies. Particularly, we focus on findings underscoring a role for galectins and glycosylated ligands in promoting resistance to anti- VEGF therapies and discuss possible strategies to overcome or attenuate this compensatory pathway. Finally, we highlight emerging evidence demonstrating the interplay between immunosuppressive and pro-angiogenic programs in the tumor microenvironment (TME) and discuss emerging combinatorial anticancer strategies aimed at simultaneously potentiating antitumor immune responses and counteracting aberrant angiogenesis.
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Authors | Diego O Croci, Santiago P Mendez-Huergo, Juan P Cerliani, Gabriel A Rabinovich |
Journal | Handbook of experimental pharmacology
(Handb Exp Pharmacol)
2018
Vol. 249
Pg. 31-61
ISSN: 0171-2004 [Print] Germany |
PMID | 28405776
(Publication Type: Journal Article)
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Chemical References |
- Chemokines
- Cytokines
- Galectins
- Vascular Endothelial Growth Factor A
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Topics |
- Chemokines
- Cytokines
- Drug Resistance, Neoplasm
- Galectins
- Humans
- Hypoxia
- Neoplasms
(drug therapy, immunology)
- Neovascularization, Pathologic
(drug therapy)
- Tumor Microenvironment
- Vascular Endothelial Growth Factor A
(antagonists & inhibitors)
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