Abstract
Medulloblastoma (MB) is the most frequent malignant brain tumor in children. Treatment of MB is based on histopathological and molecular stratification, and includes surgical intervention, often with craniospinal irradiation and adjuvant chemotherapy. Unfortunately, however, this treatment leads to a high morbidity rate, and it does not cure all patients either, with around 30% succumbing to their disease. With improved cancer genomics and better molecular characterization, MB has been classified into four major subgroups, wingless-activated, sonic hedgehog-activated, Group 3, and Group 4, with each group consisting of additional subtypes. Recently disclosed genetic drivers of MB may in the future help improve treatment, and in this way reduce therapy-related toxicity. In this review, we describe the heterogeneity of the MB subgroups, and potential new options for targeted therapy.
Highlights
Medulloblastoma (MB) is the most frequent malignant brain tumor in children
Complexity of MB has resulted in its classification into four major subgroups, wingless-activated (WNT), sonic hedgehogactivated (SHH), Group 3, and Group 4 MB, with each comprising additional subtypes (2)
We describe the heterogeneity of the MB subgroups, and some advances in targeted therapy
Summary
Despite recent advances in cancer genomics, the standard of care for all MB subgroups still generally consists of maximal surgical resection, CSI and adjuvant chemotherapy, leading to numerous severe short- and long-term side-effects. A different strategy altogether is to treat MB by immunotherapy, where the major challenge lies in the identification of new antigens to engineer therapies with simultaneously more than one target. In this way, immunosuppression can be counteracted, and the patient’s immunity activated by cancer vaccines, viruses, or T-cell therapy. As pre-clinical research is continuously driving the field forward, with large international trials, the biology of individual treatment responses is being more and more understood Using this comprehensive knowledge, targeted therapies have the potential to improve overall survival as well as the quality of life of MB survivors
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