Innovating Strategies and Tailored Approaches in Neuro-Oncology

Abstract

Diffuse gliomas, the most frequent and aggressive primary central nervous system neoplasms, currently lack effective curative treatments, particularly for cases lacking the favorable prognostic marker IDH mutation. Nonetheless, advances in molecular biology allowed to identify several druggable alterations in a subset of IDH wild-type gliomas, such as NTRK and FGFR-TACC fusions, and BRAF hotspot mutations. Multi-tyrosine kinase inhibitors, such as regorafenib, also showed efficacy in the setting of recurrent glioblastoma. IDH inhibitors are currently in the advanced phase of clinical evaluation for patients with IDH-mutant gliomas. Several immunotherapeutic approaches, such as tumor vaccines or checkpoint inhibitors, failed to improve patients’ outcomes. Even so, they may be still beneficial in a subset of them. New methods, such as using pulsed ultrasound to disrupt the blood–brain barrier, gene therapy, and oncolytic virotherapy, are well tolerated and may be included in the therapeutic armamentarium soon.

Patient, Relative and Staff Experiences of Clinical Trial Participation in Neurooncology: “Maybe You Can Also Show the Positive, No Matter How It Ends”

“… 1–3 Growing scientific insights give rise to new therapeutic targets with a shift towards targeted molecular therapies. 2 , 4 The most promising new therapeutic approaches progress into clinical trials. 1–3 …”

“…[1][2][3] Growing scientific insights give rise to new therapeutic targets with a shift towards targeted molecular therapies. 2,4 The most promising new therapeutic approaches progress into clinical trials. [1][2][3] Patients with malignant brain tumors have to cope with the heterogenous consequences of a neurological disease and cancer, sometimes called the "double threat".…”

The Neurogenome study: Comprehensive molecular profiling to optimize treatment for Danish glioblastoma patients

“…Improvement in treatment with targeted therapy has become an option for many solid tumors, even for selected GBM patients, for example, targeting of neurotrophic tyrosine receptor kinase (NTRK) or fibroblast growth factor (FGFR) fusion genes with small molecule tyrosine kinase inhibitors, and BRAF inhibition ( NCT02034110 ). 9–14 GBM can genetically alter during treatment, become more heterogenous, and develop resistant tumor clones. Therefore, a paired tumor sample at diagnosis and at relapse from the same patient can differ in clonality and genomic signature, 15–18 making a genomic profile from diagnostic tissue difficult to use for targeted treatment in the relapse setting.…”