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Review
. 2022 Feb 22;14(5):1124.
doi: 10.3390/cancers14051124.

Innovating Strategies and Tailored Approaches in Neuro-Oncology

Alberto Picca  1 , David Guyon  2 , Orazio Santo Santonocito  3 , Capucine Baldini  4 , Ahmed Idbaih  1 , Alexandre Carpentier  5 , Antonio Giuseppe Naccarato  6   7 , Mario Caccese  8 , Giuseppe Lombardi  8 , Anna Luisa Di Stefano  3   9
Affiliations
Review

Innovating Strategies and Tailored Approaches in Neuro-Oncology

Alberto Picca et al. Cancers (Basel). .

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.

Keywords: blood–brain barrier disruption; glioma; immunotherapy; molecular markers; targeted therapies.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Examples of objective responses to tyrosine kinase inhibition in patients with primary brain tumors. Panels (A–D): tumor response after two cycles of regorafenib in a 49-year-old patient with recurrent IDH wild-type GBM. Panels (E–H): tumor response after three cycles of vemurafenib in a 38-year-old patient affected by recurrent BRAF mutant anaplastic ganglioglioma (case already reported in ref. [42]). Panels (I–L): a 53-year-old patient with STRN1-NTRK2 fusion positive high grade glioneuronal tumor treated with larotrectinib and experiencing a complete tumor response (case already reported in ref. [43]).
Figure 2
Figure 2
57-year-old patient with an IDH wild-type, FGFR3-TACC3 fusion positive GBM treated at recurrence with the FGFR inhibitor erdafitinib. Brain MRI imaging at baseline (Panels A–C) and after 6 months of therapy (Panels D–F).
Figure 3
Figure 3
Adult patient with recurrent glioblastoma before (Panel A) and after (Panel B) sonication using the Sonocloud device (star) implanted in the skull. In (Panel B), contrast enhancement (arrow) indicates ultrasound mediated blood–brain barrier opening. Case already published in ref. [169].
See this image and copyright information in PMC

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