Table 5.

Potential pharmacodynamic biomarkers of antiangiogenic therapy

Biomarkers	Clinical evidence	Challenges and comments
Tumor
MRI (Ktrans)	rGBM: drop at days 1, 28, 56, 112 after cediranib Advanced HCC: drop at day 14 after sunitinib Multiple tumors: drop at day 2 after axitinib	Unclear when is the optimal time of evaluation as pharmacodynamic biomarker after anti-VEGF treatment18,22,23,77–80
MRI (Ki)	Multiple tumors: drop at day 2 after vatalanib	Unclear when is the optimal time of evaluation as pharmacodynamic biomarker after anti-VEGF treatment18,22,23,77–80
MRI (BF, BV)	rGBM: increase after treatment, decrease after treatment interruptions	Unclear when is the optimal time of evaluation as pharmacodynamic biomarker after anti-VEGF treatment18,22,23,77–80
CT (BF, BV)	Locally advanced rectal cancer: drop at day 12 and 96 after bevacizumab Advanced HCC: drop at day 12 after bevacizumab mRCC: drop at day 2 and week 18 after bevacizumab with interferon	Unclear when is the optimal time of evaluation as pharmacodynamic biomarker after anti-VEGF treatment18,22,23,77–80
IFP	Locally advanced rectal cancer: drop at day 12 after bevacizumab	Unclear when is the optimal time of evaluation as pharmacodynamic biomarker after anti-VEGF treatment. Measurement limited by lack of accessibility in some tumors22
Systemic
Plasma VEGF	Bevacizumab alone and with chemoradiation increases plasma VEGF in patients with locally advanced rectal cancer Sunitinib increases plasma VEGF in patients with mRCC Cediranib increases plasma VEGF in patients with rGBM Cediranib increases plasma VEGF in patients with solid tumors Sunitinib increases plasma VEGF in patients with mRCC Sunitinib increases plasma VEGF in patients with GISTs Sunitinib increases plasma VEGF in patients with mCRC Semaxanib with thalidomide increases serum VEGF in patients with metastatic melanoma Sunitinib increases plasma VEGF in patients with mBC Sunitinib increases plasma VEGF in patients with advanced HCC	Unclear when is the optimal time of evaluation as pharmacodynamic biomarker after anti-VEGF treatment6,18,21,22,23,32,39,49–53,58
Plasma PIGF	Bevacizumab alone and with chemoradiation increases plasma PIGF in patients with locally advanced rectal cancer Sunitinib increases plasma PIGF in patients with mRCC Cediranib increases plasma PIGF in patients with rGBM Cediranib increases plasma PIGF in patients with solid tumors Sunitinib increases plasma PIGF in patients with mRCC Sunitinib increases plasma PIGF in patients with advanced HCC	Unclear when is the optimal time of evaluation as pharmacodynamic biomarker after anti-VEGF treatment18,21,22,23,32,49,50,52,58
Plasma soluble VEGFRs	Sunitinib decreases plasma sVEGFR2 in patients with GIST Cediranib decreases plasma sVEGFR2 in patients with rGBM Cediranib decreases plasma sVEGFR2 in patients with solid tumors Sunitinib decreases plasma sVEGFR2 and sVEGFR3 in patients with mRCC Sunitinib decreases plasma sVEGFR2 and sVEGFR3 in patients with mCRC Sunitinib decreases plasma sVEGFR2 and sVEGFR3 in patients with mBC Sunitinib decreases plasma sVEGFR2 and sVEGFR3 in patients with advanced HCC	Unclear when is the optimal time of evaluation as pharmacodynamic biomarker after anti-VEGF treatment. Bevacizumab does not decrease the plasma VEGFR2 levels6,18,21,22,23,39,49,50,52,53,58
Circulating cells	Bevacizumab decreases CD31+CD45− and CD34+CD133+ cells in patients with locally advanced rectal cancer Sunitinib decreases the monocytes in patients with GISTs Sunitinib decreases CD34+CD133+ cells in patients with advanced HCC	Changes are transient and are dependent on the incorporation of cytotoxics in the regimen Unclear what population has pharmacodynamic biomarker value21,23,32

Abbreviations: BC, breast cancer; BF, blood flow; BV, blood volume; GIST, gastrointestinal stromal tumors; HCC hepatocellular carcinoma; IFP, interstitial fluid pressure; mBC, metastatic breast cancer; mCRC, metastatic colorectal cancer; mRCC, metastatic renal-cell carcinoma; PIGF, placental growth factor; rGBM, recurrent glioblastoma.