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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.
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