EGFR amplification

The presence of CDK4, CCND2, PDGFRA, PIK3R1, MYCN, and EGFR alterations result in an intermediate patient survival in IDH-mutant astrocytoma. Adding these molecular alterations should be considered in future diagnostic classification systems to improve stratification of high-risk patients.

Targeting KAT7 or HELDR markedly enhances therapeutic effects of anti-EGFR treatments for GBM. These results not only reveal the role of HELDR in EGFR-amplified GBM but also provide a strong rationale to characterize the role of lncRNAs co-amplified with driver oncogenes in human cancers.

Standard-of-care surgery, radiation, and temozolomide yield a median survival of 14-16 months in patients with glioblastoma (GBM)...NGS yielded actionable alterations targeted after conventional surgery/chemoradiation therapy: imatinib (for KIT and PDGRA amplification) and bevacizumab (for KDR [VEGFR2] amplification); everolimus (mTOR inhibitor for TSC2 and PTEN loss-of-function alterations); and ivosidenib (IDH1 inhibitor for IDH1 mutations in two cases, including the oligosarcoma). Three patients remain in radiographic and clinical remission at 39+, 48, and 52+ months; the patient with oligosarcoma showed clinical and imaging response lasting 8 months. Our exceptional responders with high-grade gliomas suggest that biomarker-matched targeted therapy can benefit select patients with high-grade glioma and warrants prospective clinical trials.

Lymphoid Enhancer-Binding Factor 1 (LEF1) immunoreactivity was identified within sarcomatous regions of gliosarcoma without detectable nuclear β-catenin, suggesting a role for β-catenin independent wingless (WNT) effector signaling in sarcomatous transformation. This study adds to the growing literature demonstrating differences in the genetic underpinning of gliosarcoma and glioblastoma, establishes feasibility of spatial transcriptomic approaches in gliosarcoma, and builds on digital spatial profiling-based results as a discovery platform to identify pathways and immunohistochemical markers for further study.

The study underscores the significance of incorporating molecular profiling into decision-making processes for patients with glioblastoma. Furthermore, stratification by recurrence patterns has the potential to enhance the efficacy of future clinical trials.

The tumor habitat imaging model based on advanced MRI was useful for accurately predicting TERT promoter mutation and EGFR amplification status in IDH wild-type glioblastoma.

P2, N=78, Recruiting, L. Nicolas Gonzalez Castro, MD, PhD | Trial completion date: Nov 2026 --> Mar 2027 | Trial primary completion date: Feb 2026 --> Aug 2026

P2, N=37, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> Dec 2026 | Trial primary completion date: May 2026 --> Dec 2026

Our study demonstrated that baseline EGFR amplification defines a clinically distinct, aggressive subtype of treatment-naïve patients with concurrent EGFR L858R mutation and EGFR amplification. Second-generation TKIs showed superior efficacy over third-generation TKIs in this specific population. These findings refine prognostic stratification and support biomarker-guided first-line therapy selection for EGFR L858R-mutant NSCLC with co-occurring EGFR amplification.

Metabolic subtyping identifies DEMs as critical drivers of glioma progression. The DEM-derived risk model, combined with EGFR/IDH status, provides a clinically actionable tool for prognosis and targeted therapy development.

This study represents the largest genomic cohort to date of FGFR alterations in GBM, IDH-wt. FGFR::TACC fusion-positive and FGFR1 mutation-positive GBMs exhibited distinct genetic profiles, highlighting the clinical relevance of molecular subclassification and providing insight for future therapeutic strategies.