Table 2.

Therapeutic targeted molecules in the tumor microenvironment

Molecular target	Drug name	Clinical triala	References
Basic Wbroblast growth factor	Interferon-alpha	II and III	Kerbel and Folkman [81]
Endothelial microtubules	Combretastatin A4 phosphate	II	Young and Chaplin [82]
Endothelin A receptor	Atrasentan	II	Jimeno and Carducci [83]
Fibroblast activation protein	Sibrotuzumab	I	Scott et al. [75]
Hypoxia-inducible factor 1α	2-Methoxyestradiol (2-ME2)	I	Mooberry [84]
Integrin α5β1	Volociximab (M200)	II	Jin and Varner [85]
Integrin ανβ3	Vitaxin	II	Gutheil et al. [86]; Jin and Varner [85]
Integrin ανβ3 and ανβ5	Cilengitide (EMD121974)	I and II	Burke et al. [87]
MMP-2, MMP-9 and MMP-12	Neovastat (AE-941)	III	Gingras et al. [88]
NFκB, TNFα, IL-6 and VEGF	Thalidomid (Thalidomide)	III	Bartlett et al. [89], Sleijfer et al. [90]
NFκB, TNFα, IL-6 and VEGF	CC-5013 (Revimid)	II and III	Bartlett et al. [89], Sleijfer et al. [90]
PDGFR, c-Kit and Tyrosine kinases	Gleevec (Imatinib Mesylate)	FDA-approved	Druker et al. [91], Pietras et al. [92]
Protein kinase cβ	Enzastaurin (LY-317615)	II	GraV et al. [93]
Tyrosine kinase, VEGFR, and CSF-1R	SU11248	II	Mendel et al. [94], Pietras and Hanahan [95]
Vascular endothelial growth factor	Avastin (Bevacizumab)	FDA-approved	Ferrara et al. [96], Hurwitz et al. [97]
Vascular endothelial growth factor	Neovastat (AE-941)	III	Gingras et al. [88]
Vascular endothelial growth factor A	VEGF-Trap	I and II	Holash et al. [98]
Vascular endothelial growth factor receptor	Vatalanib (PTK787/ZK 222584)	II and III	Manley et al. [99]; Morgan et al. [100]
Vascular endothelial growth factor receptor 2	Vandetanib (ZD6474)	I and II	Wedge et al. [101]

MMP matrix metalloproteinase, VEGF vascular endothelial growth factor, VEGFR vascular endothelial growth factor receptor, NFκB nuclear factor of κB, TNF tumor necrosis factor, IL interleukin, PDGFR platelet-derived growth factor receptor, CSF-1R colony-stimulating factor receptor

^aPhase of therapeutic agents in clinical trial or approved by FDA