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<p>Molecular characterization has profoundly changed the understanding of glioblastomas and opened new therapeutic avenues. Numerous genetic alterations—such as those in <i>EGFR</i>, <i>NF1</i>, <i>PIK3CA</i>, <i>CDKN2A/B</i>, <i>RB1</i>, and <i>BRAF p.V600E</i> (particularly in epithelioid subtypes)—are frequently detected. While the <i>BRAF p.V600E</i> mutation represents a&#xa0;validated therapeutic target for BRAF/MEK inhibition, the clinical benefit of other targeted therapies continues to be investigated. Molecular testing is especially recommended for patients who have exhausted standard treatment options, in order to identify eligibility for clinical trials or prospective registries. Targeted panel-based next-generation sequencing (NGS) has become the preferred diagnostic approach, as many relevant alterations are rare and often mutually exclusive. NGS is feasible in the management of glioblastomas in clinical practice. A&#xa0;substantial proportion of patients carry molecular alterations of potential therapeutic relevance. Differences in mutation frequency between primary and recurrent tumors highlight the importance of repeated molecular profiling during disease progression. Despite these advances, effective treatment options are still lacking for glioblastomas. Precision oncology approaches are particularly effective in tumors with oncogenic drivers and are currently only clinically established in molecularly defined subgroups. Further prospective studies are needed to validate the clinical relevance of molecular targets and to develop precision medicine treatment pathways.</p>

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Die molekularen Gesichter des Glioblastoms

  • 期刊论文

  • 发表日期：

    2025年8月15日

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  • Tadeja Urbanic Purkart

摘要

Molecular characterization has profoundly changed the understanding of glioblastomas and opened new therapeutic avenues. Numerous genetic alterations—such as those in EGFR, NF1, PIK3CA, CDKN2A/B, RB1, and BRAF p.V600E (particularly in epithelioid subtypes)—are frequently detected. While the BRAF p.V600E mutation represents a validated therapeutic target for BRAF/MEK inhibition, the clinical benefit of other targeted therapies continues to be investigated. Molecular testing is especially recommended for patients who have exhausted standard treatment options, in order to identify eligibility for clinical trials or prospective registries. Targeted panel-based next-generation sequencing (NGS) has become the preferred diagnostic approach, as many relevant alterations are rare and often mutually exclusive. NGS is feasible in the management of glioblastomas in clinical practice. A substantial proportion of patients carry molecular alterations of potential therapeutic relevance. Differences in mutation frequency between primary and recurrent tumors highlight the importance of repeated molecular profiling during disease progression. Despite these advances, effective treatment options are still lacking for glioblastomas. Precision oncology approaches are particularly effective in tumors with oncogenic drivers and are currently only clinically established in molecularly defined subgroups. Further prospective studies are needed to validate the clinical relevance of molecular targets and to develop precision medicine treatment pathways.