Glioblastoma targeted therapy: updated approaches from recent biological insights
Cette étude passe en revue les essais cliniques évaluant l'efficacité de thérapies ciblées et d'immunothérapies pour traiter les patients atteints d'un glioblastome et analyse les enjeux liés au développement de ces agents thérapeutiques
Glioblastoma (WHO grade IV astrocytoma) is the most frequent primary brain tumor in adults, representing a highly heterogeneous group of neoplasms that are among the most aggressive and challenging cancers to treat. An improved understanding of the molecular pathways that drive malignancy in glioblastoma has led to the development of various biomarkers and the evaluation of several agents specifically targeting tumor cells and the tumor microenvironment. A number of rational approaches are being investigated, including therapies targeting tumor growth factor receptors and downstream pathways, cell cycle and epigenetic regulation, angiogenesis and antitumor immune response. Moreover, recent identification and validation of prognostic and predictive biomarkers have allowed implementation of modern trial designs based on matching molecular features of tumors to targeted therapeutics. However, while occasional targeted therapy responses have been documented in patients, to date no targeted therapy has been formally validated as effective in the clinical neuro-oncology setting. The lack of knowledge about the most relevant molecular drivers in vivo combined with a lack of highly bioactive and brain penetrant-targeted therapies remain significant challenges. In this article, we review the most promising biological insights that have opened the way for the development of targeted therapies in glioblastoma, and examine the recent data from clinical trials evaluating targeted therapies and immunotherapies. We discuss the challenges and opportunities for the development of these agents in glioblastoma