Diffuse Gliomas with FGFR3-TACC3 Fusions: Oncogenic Mechanisms, Hallmarks, and Therapeutic Perspectives

In 2012, whole-transcriptome sequencing analysis led to the discovery of recurrent fusions involving the and genes as the main oncological driver in a subset of human glioblastomas. Since then, fusions have been identified in several other solid cancers. Further studies dissected the oncogenic mechanisms of the fusion protein and its complex interplay with cancer cell metabolism. fusion-driven gliomas emerged as a defined subgroup with specific clinical, histological, and molecular features. Several inhibitors were tested in fusion-positive gliomas and proved some efficacy, although inferior to the results seen in other fusion-driven cancers. In this review, we summarize and discuss the state-of-the-art knowledge resulting from a 10-year research effort in the field, its clinical implications for glioma patients, the potential reasons for targeted therapy failures, and the perspective of emerging treatments.