Knowledge-based treatment in uveal melanoma

Filali, M. el (2012)

Doctoral Thesis

Uveal melanoma (UM) is a disease with many faces: ophthalmologists treat the primary tumor, but the patient faces the problem of developing metastases, which are often deadly after a short period. Recent insight, indicates the need for knowledge-based treatment of UM. The __pseudohypoxic__ and tumor promoting effects of bevacizumab as described in this thesis is especially relevant. Bevacizumab is frequently used off-label to treat macular edema in UM patients suffering of radiation retinopathy, without the knowledge of possible effect on still viable UM cells. We further observed that specific peptides, such as UMAP1, which can successfully be internalized by targeted UM cells, have demonstrated potential for UM-targeted treatment. These peptides have to be investigated in vivo, to ascertain whether they are a viable clinical tool. Labeling the peptides with radionuclides, and demonstrating specificity for UM cells are some of the challenges which have to be overcome. Another aspect in the patient-specific treatment of UM is the in vitro analysis of primary UM samples to predict treatment responses. In case of Dasatinib, we describe treatment responses associated with monosomy 3 and __kinase__ activity in different primary UM samples.

• Targeted therapy
• Dasatinib
• Bevacizumab
• Angiogenesis
• VEGF
• Uveal melanoma

• All authors: Filali, M. el
• Supervisor: Luyten, G.P.M.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2012-05-22
• ISBN (print): 9789461692375