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PhD theses

Movies

Funding

Research line III: Combination therapies

 

Angiogenesis and radiotherapy

Our aim is to gain insight in the mechanisms involved in the interaction between angiostatic therapy and to determine the optimal scheduling scheme for combination therapy in the clinical setting. 

Apart from direct effects on the tumor vasculature, angiogenesis inhibitors also improve the response to radiotherapy (Dings, Int J Cancer, 2005; Dings, Cancer Res, 2003). This beneficial effect is caused by a short period of vessel normalization which improves blood flow and oxygenation (Dings et al., Clin Cancer Res, 2007;). Little is known regarding the cellular mechanisms that underlie the response to combination therapy. Furthermore, it is important to determine the normalization window of angiostatic agents in order to optimize combination therapy.

 

 

 

Combination of radiotherapy and anti-angiogenesis gives synergistic anti-tumor effect. Results give way to the hypothesis of vascular normalization. 

From Dings et al., Clin. Cancer Res. 2007.  

 

Angiogenesis and immunotherapy

We investigate the relationship between angiogenesis and the immune system. The ultimate goal is to investigate whether angiogenesis inhibition can be used to improve immunotherapy.

Endothelial cell adhesion molecules like intercellular adhesion molecule-1 (ICAM-1) are suppressed by angiogenic growth factors such as bFGF and VEGF (Griffioen et al. Cancer Res. 56:1111, 1996). This leads to tumor escape from immunity (Dirkx et al. FASEB J. 2006). Angiostatic factors can therefore improve immunotherapy (Dings et al. Clin. Cancer Res. 2011).
Links below show video images of leukocyte vessel wall interactions in:

normal control tissue

tumor tissue

tumor tissue of mice treated with anginex

 

Relationship between angiogenesis inhibition and leukocyte infiltration. From Drikx et al. FASEB J., 2006.

 

Angiogenesis and photodynamic therapy

Photodynamic therapy induces an angiogenic response in the treated tissue. Combination with angiogenesis inhibition is therefore a promising strategy against cancer

 

Angiography images of the CAM before (left) and 48h after PDT (right). Efficacy of the combination of PDT with Avastin is shown in lower right panel.

From Nowak-Sliwinska et al. Angiogenesis 2010.