< Back to previous page

Project

Evaluation of the therapeutic value of asparaginase for the treatment of glioblastoma

Asparaginase (ASNase) is an enzyme that hydrolyses the amino acid asparagine into aspartic acid and ammonia. Currently, ASNase serves as a cornerstone drug for the treatment of acute lymphoblastic leukemia (ALL) in children. Indeed, these leukemic cells lack the expression of asparagine synthetase, the enzyme responsible for the production of asparagine, and therefore entirely dependent on extracellular asparagine for their leukemic survival. The reduction of exogenous asparagine by administration of ASNase will cause the malignant cells to die. Glioblastoma (GBM; astrocytoma Grade IV) is the most common type of brain tumour in adults and is characterized by an extremely poor clinical outcome. Indeed, 5-year overall survival for this disease is less than 10%. Furthermore, and despite important advances in understanding the molecular pathogenesis and biology of these tumours, the standard-of-care for GBM has not changed over the last 15 years and still consists of maximal surgical resection combined with radiation therapy and temozolomide treatment, an alkylating chemotherapy. Despite multiple clinical trials were conducted based on new therapeutic strategies, none of these new therapies showed a clear clinical benefit. Therefore, design of novel therapeutic strategies for the treatment of this tumour type are urgently needed. Notably, recent reports have suggested that ASNase might also have clinical potential for the treatment of human GBM, especially in combination with cytotoxic chemotherapeutics. However, the toxicity of the standard ASNase for adults is limiting its use. New variants of ASNase with better toxicity profiles were recently developed, but are not yet assessed for the potential treatment of GBM. Therefore, in this PhD project, we will use multiple ASNase variants in combination with chemotherapy to test them in both in vitro and in vivo models for GBM, in newly diagnosed and recurrent settings. The goal is to acquire the necessary insight into the molecular and pathological mechanisms of this new treatment as a preparation of a potential clinical trial.

Date:30 Mar 2021 →  Today
Keywords:Glioblastoma, Asparaginase
Disciplines:Cancer therapy
Project type:PhD project