Table 3 Therapeutic agents targeting VM

Brucine

Triple-negative breast cancer

EphA2/MMP-2/MMP-9

Suppresses VM by disrupting F-actin cytoskeleton and microtubule structure

[111]

R8 modified epirubicin-dihydroartemisinin liposomes

Non-small-cell lung cancer

VE-cadherin/TGF-β/MMP-2/HIF-1

Suppresses VM channels and tumor metastasis by downregulating the levels of VE-cad, TGF-β, MMP-2 and HIF-α

[115]

Ginsenoside Rg3

Pancreatic cancer

VE-cadherin/EphA2/MMP-2/MMP-9

Downregulates the levels of VE-cad, EphA2, MMP-2 and MMP-9 to inhibit the formation of VM

[116]

Dequalinium (DQA) modified paclitaxel plus ligustrazine micelles

Non-small-cell lung cancer

VEGF/MMP-2/ TGF-β/E-cadherin

Destroies VM channels and down regulate the expression of VEGF, MMP-2, TGF-β and E-cadherin

[122]

Favone isoxanthohumol

Breast cancer

IFN-γ/IL-4/IL-6 Jak/Stat signaling

Blocks IFN-γ/IL-4/IL-6 Jak/Stat signaling and TGF-β signaling to inhibits VM formation

[112]

Dunorubicin and dioscin codelivery liposomes

Non-small-cell lung cancer

MMP-2/VE-cadherin TGF-β/HIF-1α

Inhibits VM formation by down regulating the levels of MMP-2, VE-cadherin, TGF-β and HIF-1α

[117]

Melittin

Liver cancer

HIF-1α/Akt

Inhibits hypoxia-induced VM formation and EMT by suppressing HIF-α/Akt pathway

[118]

Tivantinib (TivB)

Melanoma

Vnculin/RhoC

Disrupts VM channels by targeting vinculin and RhoC

[114]

PARP inhibition

Melanoma

VE-cadherin

Inhibits reduced pro-metastatic markers

[110]

Thalidomide

Melanoma

VEGF/NF-ΚB/MMP-2/MMP-9

Regulates vasculogenic factors to inhibit VM channel and mosaic vessels formation

[119]

Trastuzumab

HER2-positive breast cancer

VEGF

Suppresses VM in HER2-positive BCCs

[113]

Rapamycin

Ovarian cancer

VEGF/mTOR

As HIF-α inhibitor to prevent VM

[120]

Resveratrol

Melanoma

VEGF-R1/VEGF-R2

Suppresses VM formation

[121]

Niclosamide

Oral cancer

miR-124/STAT3

Inhibits VM formation through downregulation of the expression of VM-related genes VEGFA, MMP2, ROCK1, and Cdc42

[123]

Celastrus orbiculatus extrac (COE)

Hepathocellular carcinima

Notch1 signaling

Inhibits VM formation by downregulating Notch 1 signaling

[83]

Luteolin

Gastric cancer

Notch 1/VEGF

Inhibits VM formation through suppressing VEGF secretion dependent on Notch1 expression

[69]