Angiogenesis in mesothelioma

Buikhuisen, W.A. (2021)

Doctoral Thesis

Malignant mesothelioma is a cancer, often originating from the pleura of the chest. There are no curative treatment options and systemic palliative treatments are scarce. It is suspected that the growth process in mesothelioma is highly dependent on the creation of new vessels stimulated by the tumour itself, also called angiogenesis. In this thesis, 2 drugs that inhibit angiogenesis were tested aiming at improving progression-free survival (PFS). Thalidomide was given as a maintenance treatment after first-line chemotherapy in a large randomised study. Axitinib was given in combination with first-line chemotherapy in a smaller randomised trial, in which we included pre- and post-treatment biopsies. The vascularisation of the tumour and the possible influence of vascular growth factors were examined. In the translational part of this study, we showed that axitinib treatment efficiently prevented tumour neovascularisation. However, this did not improve PFS. The thalidomide study also showed no benefit in PFS or survival. Meanwhile the literature has shown that many angiogenesis inhibitors do not achieve a positive result either. We will have to look for other treatment options to improve the prognosis of mesothelioma patients.

• Mesothelioma
• Systemic treatment
• Vascular endothelial growth factor (VEGF)
• Neovascularisation
• Microvessel density

• All authors: Buikhuisen, W.A.
• Supervisor: Baas, P.
• Co-supervisor: Burgers, J.A.
• Committee: Hiemstra, P.S.; Marijnen, C.A.M.; Van Meerbeeck, J.P.; Popat, S.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2021-06-02
• ISBN (print): 9789464232622