International tumor board explores personalized treatment options for glioblastoma with MDM2 and EGFR amplifications

“This case underscores the immense complexity of treating GBM.”

BUFFALO, NY - October 22, 2026 – A new case report was published in Volume 17 of Oncotarget on October 16, 2026, titled “Case Report WIN-MTB-2024001 – WIN International Molecular Tumor Board: A 55-year-old male with glioblastoma exhibiting amplifications in MDM2 and EGFR.”

The report describes the clinical journey of a 55-year-old man diagnosed with glioblastoma (GBM), an aggressive brain cancer, whose tumor carried amplifications of the MDM2 and EGFR genes alongside other molecular alterations. Through comprehensive genomic profiling and an international molecular tumor board, the case highlights how precision oncology may identify potential treatment strategies when standard therapies offer limited long-term control.

The report was led by first and corresponding author Oncotarget Editor-in-Chief Dr. Wafik S. El-Deiry, affiliated with the Worldwide Innovative Network (WIN) Consortium and the Legorreta Cancer Center at Brown University. Equal-contributing author Razelle Kurzrock is affiliated with the WIN Consortium and the Medical College of Wisconsin.

Glioblastoma is among the most aggressive primary brain tumors in adults, characterized by rapid growth, extensive infiltration into surrounding tissue and frequent recurrence. Standard treatment generally combines maximal safe surgical resection, radiotherapy and temozolomide chemotherapy. However, median survival remains approximately 15 months, underscoring the need for additional therapeutic approaches.

One major challenge is molecular heterogeneity, meaning that tumors can contain genetic alterations that influence growth, treatment response and resistance. Next-generation sequencing (NGS) can help identify these abnormalities and reveal potential targets for individualized treatment.

The patient initially experienced dizziness and a generalized seizure in February 2023, followed by impaired speech. Brain imaging revealed a small mass in the left temporal lobe. Following another seizure in June 2023, imaging showed tumor growth, prompting an anterior temporal lobectomy and amygdalohippocampectomy. Histopathological examination confirmed glioblastoma.

Molecular profiling revealed an IDH-wildtype tumor with an unmethylated MGMT promoter, a feature generally associated with reduced benefit from temozolomide compared with MGMT-methylated tumors. Additional testing identified EGFR and MDM2 amplifications, a CDKN2A frameshift alteration and other genomic abnormalities.

MDM2 regulates p53, a tumor-suppressor protein involved in controlling cell division and eliminating damaged cells. Its amplification can weaken p53-mediated tumor suppression, potentially promoting cancer-cell survival and treatment resistance. EGFR amplification can activate signaling pathways that support tumor growth and invasion, while CDKN2A alterations disrupt cell-cycle regulation through the p16–CDK4/6–RB pathway. Together, these findings provided a rationale for investigating therapies targeting multiple molecular vulnerabilities.

Comprehensive testing consistently identified MDM2 and EGFR amplification but produced conflicting results regarding microsatellite instability. One analysis classified the tumor as microsatellite stable, while another indicated instability. Because this discrepancy was not resolved through confirmatory testing, its potential implications for immunotherapy remained uncertain.

Following surgery, the patient received radiotherapy and temozolomide. In September 2023, he enrolled in a phase II clinical trial involving paxalisib, an investigational PI3K/mTOR inhibitor, combined with a ketogenic diet and metformin. At the time of the molecular tumor board discussion, the patient was in remission while receiving this experimental approach. However, the report does not establish which component of his overall treatment contributed to disease control.

The patient was also considering personalized neoantigen vaccine therapy, an investigational approach designed to stimulate immune responses against tumor-specific mutated peptides. The report does not indicate that the vaccine had been administered.

To identify options in the event of recurrence, the WIN Consortium International Molecular Tumor Board brought together precision oncology specialists from 18 organizations across 13 countries. The experts evaluated the patient's clinical history, genomic findings and tumor microenvironment to explore potential targeted and immune-based therapies.

One strategy involved EGFR inhibitors, including investigational agents designed to reach tumors within the central nervous system. The board discussed ERAS-801 and possible combinations involving osimertinib or lapatinib with the EGFR-targeting antibody cetuximab. However, their effectiveness in this patient's tumor was not established, and access would depend on clinical trial availability and eligibility.

The experts also considered MDM2 inhibitors, including navtemadlin, idasanutlin and milademetan, as potential approaches to restoring p53-mediated tumor suppression. Because these agents are not approved for GBM, their use would remain investigational and require appropriate clinical trial or regulated access.

Another proposed strategy involved combining EGFR-targeted therapy with CDK4/6 inhibition to address both EGFR amplification and CDKN2A loss. Abemaciclib, a CDK4/6 inhibitor with demonstrated central nervous system penetration, was discussed as a possible component. These combinations remain proposed treatment options rather than therapies validated in the reported patient.

Immunotherapy presented additional challenges. The molecular tumor board discussed evidence linking MDM2 and EGFR alterations to resistance or accelerated tumor progression during immune checkpoint blockade in selected cancers. However, these associations do not establish that similar outcomes would occur in this patient.

The tumor microenvironment showed substantial CD4 and CD8 T-cell infiltration, alongside regulatory T cells and moderate PD-L1 expression. These findings suggested immune activity but also potential immune suppression, raising questions about whether combining targeted treatments with immunotherapy might improve responses. Such approaches require further investigation.

The board also discussed teserpaturev (Delytact), a genetically modified herpes simplex virus designed to destroy tumor cells and stimulate antitumor immune responses. Although available in Japan under specific regulatory conditions, its potential benefit for this patient remained uncertain.

“This case emphasizes the importance of personalized treatment strategies for GBM and the need for ongoing clinical research to explore novel therapeutic options.”

The report further highlights the importance of interpreting molecular findings cautiously. For example, CDKN2A alterations raised the possibility of concurrent MTAP loss, which could offer opportunities for additional targeted approaches. However, MTAP status was not confirmed, and further testing would be necessary before considering therapies directed at this vulnerability.

As a single-patient case report, the findings cannot establish the effectiveness of the proposed treatments or determine whether specific genetic alterations predict clinical responses. The patient was in remission at the time of discussion, and the additional targeted combinations were considered as future options rather than administered therapies. The conflicting microsatellite instability results also demonstrate the importance of confirmatory testing.

The tumor board prioritized clinical trial enrollment if the disease recurred, particularly trials evaluating EGFR-directed therapies, MDM2 inhibition, immune-modulating strategies or biomarker-matched combinations. These approaches remain investigational and require prospective evaluation to establish their safety and effectiveness.

Overall, the report illustrates how international molecular tumor boards can integrate genomic profiling, clinical information and emerging therapeutic research to identify personalized treatment opportunities. While the proposed strategies require further validation, the case highlights the potential value of multidisciplinary collaboration in managing complex cancers such as glioblastoma.

DOI: https://doi.org/10.18632/oncotarget.28920 

Correspondence to: Wafik S. El-Deiry - wafik_el-deiry@brown.edu 

Abstract video: https://www.youtube.com/watch?v=s8L4gukgKWU

Keywords: cancer, precision oncology, molecular tumor board, glioblastoma

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