Angiostasis-induced vascular normalization can improve photodynamic therapy

Abstract

In a recent issue, Cellular and Molecular Life Sciences published on the combination of photodynamic therapy (PDT) and anti-angiogenesis for the treatment of cancer [1]. In this paper, Bhuvaneswari and colleagues elegantly review this field. The idea behind combining these two therapeutic strategies is based on the observation that PDT can lead to vessel closure, and hence hypoxia, as well as other tissue damage resulting in inflammation. This combination of hypoxia and inflammation can in turn cause the enhanced release of angiogenic growth factors (vascular endothelial growth factor, VEGF) followed by the regrowth of the targeted neoplastic tissue. Thus, it appeared logical to try to block the VEGF pathways after PDT, for instance by applying antibodies against VEGF. This type of combination therapy is not limited to the treatment of cancer. Indeed, for the treatment of certain forms of exudative macular degeneration, recently published results from a phase II clinical study demonstrate great promise for the combination of PDT (Visudyne) together with anti-VEGF-A therapy using humanized antibody fragments (Lucentis). PDT as a monotherapy has clearly been shown to be effective in treating some early stage superficial cancers. However, for more advanced cancers, where PDT monotherapy appears to be less effective, the usefulness of the photodynamic approach followed by anti-VEGF therapy has not yet been extensively demonstrated in the clinic.