, Volume 20, Issue 2, pp 245–267 | Cite as

Epigenetic approach for angiostatic therapy: promising combinations for cancer treatment

  • Robert H. Berndsen
  • U. Kulsoom Abdul
  • Andrea Weiss
  • Marloes Zoetemelk
  • Marije T. te Winkel
  • Paul J. Dyson
  • Arjan W. Griffioen
  • Patrycja Nowak-SliwinskaEmail author
Review Paper


Cancer cells are often dependent on epigenetic pathways for their survival. Consequently, drugs that target the epigenome, rather than the underlying DNA sequence, are currently attracting considerable attention. In recent years, the first epigenetic drugs have been approved for cancer chemotherapy, mainly for hematological applications. Limitations in single-drug efficacies have thus far limited their application in the treatment of solid tumors. Nevertheless, promising activity for these compounds has been suggested when combined with other, distinctly targeted agents. In this review, we discuss the anti-angiogenic activity of histone deacetylase and DNA methyltransferase inhibitors and their combinations with other targeted (anti-angiogenic) therapeutics in treatment of solid tumors. The role that these inhibitors play in the inhibition of tumor angiogenesis, particularly in combination with other targeted agents, and the advantages they present over broad acting anticancer agents, are critically discussed.


Anti-angiogenesis Clinical trials Combination therapy Epi-drugs Histone deacetylase inhibitors DNA methyltransferase inhibitors Solid tumors Tumor vasculature 







Acute myeloid leukemia


Azacitidine, 5-AZA-CR, 5-azacytidine


Basic fibroblast growth factor


Fibroblast growth factor receptor


Chorioallantoic membrane of the chicken embryo


Cutaneous T cell lymphoma


Cysteine-rich angiogenic inducer 61


Decitabine, 5-AZA-2′-deoxycytidine, 5-AZA-CdR


DNA methyltransferase


Epithelial cadherin


Endothelial cells


Epigallocatechin gallate


Epidermal growth factor


Epidermal growth factor receptor


Endothelial nitric oxide synthase (eNOS)


Fatty acid oxidation


Feedback system control




Histone deacetylase


Hypoxia-inducible factor 1 alpha


Human umbilical vein endothelial cells




The half maximal inhibitory concentration


Insulin-like growth factor 1






Noncoding microRNA


Matrix metalloproteinase


Metastasis-associated protein 1


Mechanistic target of rapamycin


Microvessel density




NADPH oxidase 4


Non-small cell lung cancer


Nucleosome remodeling and deacetylase


Overall survival


p300 histone acetyltransferase




Platelet-derived growth factor subunit B


Platelet-derived growth factor subunit B receptor


Progression-free survival


Poliovirus receptor-related 2






Renal cell carcinoma




S-adenosyl methionine


Small interfering RNA


Histone deacetylase sirtuins


Transforming growth factor beta


Tissue inhibitor of matrix metalloproteinase 3


Angiopoietin 1 receptor


Tyrosine kinase inhibitor


Trichostatin A


Tumor suppressor gene


Thrombospondin 1


Vascular endothelial growth factor


Vascular endothelial growth factor receptor


Vascular endothelial cadherin


Von Hippel–Lindau


Valproic acid


Wnt inhibitory factor 1





We thank the European Research Council (ERC-StG-2015-680209 to PNS) and the Dutch Cancer Society (VU2014-7234 to AWG and PNS) for financial support.


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Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  • Robert H. Berndsen
    • 1
  • U. Kulsoom Abdul
    • 1
  • Andrea Weiss
    • 2
  • Marloes Zoetemelk
    • 2
  • Marije T. te Winkel
    • 1
  • Paul J. Dyson
    • 3
  • Arjan W. Griffioen
    • 1
  • Patrycja Nowak-Sliwinska
    • 2
    Email author
  1. 1.Department of Medical OncologyVU University Medical CenterAmsterdamThe Netherlands
  2. 2.School of Pharmaceutical SciencesUniversity of GenevaGenevaSwitzerland
  3. 3.Institute of Chemical Sciences and EngineeringSwiss Federal Institute of TechnologyLausanneSwitzerland

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