Angiogenesis

, 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-Sliwinska
Review Paper

Abstract

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.

Keywords

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

Abbreviation

5FD

5-Fluoro-2′-deoxycytidine

Ang-2

Angiopoietin2

AML

Acute myeloid leukemia

AZA

Azacitidine, 5-AZA-CR, 5-azacytidine

bFGF

Basic fibroblast growth factor

FGFR

Fibroblast growth factor receptor

CAM

Chorioallantoic membrane of the chicken embryo

CTCL

Cutaneous T cell lymphoma

CYR61

Cysteine-rich angiogenic inducer 61

DAC

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

DNMT

DNA methyltransferase

E-cadherin

Epithelial cadherin

EC

Endothelial cells

EGCG

Epigallocatechin gallate

EGF

Epidermal growth factor

EGFR

Epidermal growth factor receptor

eNOS

Endothelial nitric oxide synthase (eNOS)

FAO

Fatty acid oxidation

FSC

Feedback system control

HAT

Acetyltransferase

HDAC

Histone deacetylase

HIF-1α

Hypoxia-inducible factor 1 alpha

HUVEC

Human umbilical vein endothelial cells

HYD

Hydralazine

IC50

The half maximal inhibitory concentration

IGF1

Insulin-like growth factor 1

IL

Interleukin

KP1019

trans-[Tetrachlorobis(1H-indazole)ruthenate(III)

miRNA

Noncoding microRNA

MMP

Matrix metalloproteinase

MTA1

Metastasis-associated protein 1

mTOR

Mechanistic target of rapamycin

MVD

Microvessel density

NAMI-A

trans-[Tetrachloro(dimethylsulfoxide)(imidazole)ruthenate(III)]

NOX4

NADPH oxidase 4

NSCLC

Non-small cell lung cancer

NuRD

Nucleosome remodeling and deacetylase

OS

Overall survival

p300-HAT

p300 histone acetyltransferase

PBA

Phenylbutyrate

PDGF-B

Platelet-derived growth factor subunit B

PDGFR-B

Platelet-derived growth factor subunit B receptor

PFS

Progression-free survival

PVRL2

Poliovirus receptor-related 2

RAPTA-C

Ru(η6-p-cymene)(pta)Cl2

RAPTA-T

Ru(η6-toluene)(pta)Cl2

RCC

Renal cell carcinoma

SAHA

Vorinostat

SAM

S-adenosyl methionine

siRNA

Small interfering RNA

SIRT

Histone deacetylase sirtuins

TGF-β

Transforming growth factor beta

TIMP3

Tissue inhibitor of matrix metalloproteinase 3

Tie-2

Angiopoietin 1 receptor

TKI

Tyrosine kinase inhibitor

TSA

Trichostatin A

TSG

Tumor suppressor gene

TSP-1

Thrombospondin 1

VEGF

Vascular endothelial growth factor

VEGFR

Vascular endothelial growth factor receptor

VE-cadherin

Vascular endothelial cadherin

VHL

Von Hippel–Lindau

VPA

Valproic acid

WIF-1

Wnt inhibitory factor 1

ZEB

Zebularine

Notes

Acknowledgements

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
  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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