On trail for glioma therapy?

PhD ceremony: Mr. J.M.A. Kuijlen, 13.15 uur, Academiegebouw, Broerstraat 5, Groningen

Thesis: On trail for glioma therapy?

Promotor(s): prof. J.J.A. Mooij, prof. L.F.M.H. de Ley

Faculty: Medical Sciences

Despite conventional treatment protocols (surgery, radiotherapy and chemotherapy), is the prognosis for patients with a glioblastoma, extremely poor. There is an urgency to develop new treatment strategies to improve outcome. Escapism of apoptosis, the intrinsic suicide program of the cell, is a hallmark of human cancer. Defects in apoptosis may confer resistance to therapy because most current treatment approaches initiate cell death through activation of an apoptosis pathway. Current attempts to improve the survival of glioblastoma patients will have to include strategies that specifically target tumor cell resistance to apoptosis. Of interest for GBM therapy is the selective induction of apoptosis using the pro-apoptotic tumor necrosis factor-related apoptosis inducing ligand (TRAIL).

TRAIL acts primarily through induction of the extrinsic apoptosis pathway in contrast to chemo and radiotherapy who act through the intrinsic mitochondrial pathway. This thesis elucidates TRAIL as a potential anti-neoplastic drug as TRAIL can bypass intrinsic (mitochondrial) resistance of tumor cells by acting its death inducing effect through the extrinsic pathway, evidently without causing systemic toxicity. Therefore TRAIL might be a new adjuvant therapy in the battle against GBM.