Table 1.

Summary of vascular normalization therapeutics

Drugs/therapies	Mechanism of action	Cell lines or target disease	Limitations	References
VEGF antibody (Bevacizumab)	Neutralization of VEGF	Colorectal cancer and many solid cancers	No significant clinical benefit with monotherapy. Recur tumor hypoxia. Normalization window determination needed	Carmeliet and Jain (2011), Giantonio et al. (2007)
Oxygen microbubbles	Tissue oxygenation	Transgenic prostate adenocarcinoma mouse model	Not effective in tumor diameter over 8 mm	Ho et al. (2019)
VEGFR2 antibody (Ramucirumab for human, DC101 for rat)	Neutralization of VEGFR2	Advanced breast cancer, gastroesophgeal junction carcinoma, hepatocellular carcinoma, metastatic colorectal cancer, non small cell lung cancer	Hypertension	Aprile et al. (2014), Spratlin et al. (2010), Shigeta et al. (2020), Tong et al. (2004), Chauhan et al. (2012)
Everolimus	Inhibition of mTORC1 and HIF-1	Gastric cancer, hepatocellular carcinoma, lymphoma, advanced breast cancer	Patient genome dependence	Atkins et al. (2004)
ABTAA	TIE-2 activation and ANG-2 neutralization	Mouse glioma, breast and lung cancers	No clinical study	Park et al. (2016)
COMP-ANG-1	ANG1 analog TIE-2 activation	Retina vessels	No clinical study	Hwang et al. (2009)
DAAP	Targeting both ANG-2 and VEGF	Mouse ovarian cancer	No clinical study	Koh et al. (2010)