Oncotarget. 2026 Oct 16. 17(1):
462-475
Wafik S El-Deiry,
Sadakatsu Ikeda,
Shai Magidi,
Catherine Bresson,
Hikmat Abdel-Razeq,
Anthony Joshua,
Alberto Hernando-Calvo,
Arjun Oberoi,
Zhihuang Hu,
Tobias Meissner,
Rachel Elsey,
Amal Al-Omari,
Fanny Wunder,
Razelle Kurzrock.
Copyright: © 2026 El-Deiry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The WIN Consortium International Molecular Tumor Board brings together precision oncology experts from 18 organizations in 13 countries across four continents and provides discussion for patients with cancer across the world. This case report details the medical journey of a 55-year-old man diagnosed with high-grade glioblastoma (GBM), characterized by amplifications of MDM2 and EGFR, alongside other critical genomic alterations, including a CDKN2A frameshift mutation. Despite the aggressive nature of GBM, the patient was in remission following a combination of radiotherapy and chemotherapy, surgery and participation in a phase II clinical trial (PI3K/mTOR inhibitor) combined with ketogenic diet and metformin. However, the patient was also considering personalized neoantigen vaccine therapy targeting tumor-specific mutated peptides as part of his treatment strategy. This case underscores the immense complexity of treating GBM. Next generation sequencing showed MDM2 amplification, which hinders the tumor-suppressive functions of p53, and EGFR amplification, which promotes oncogenic signaling. The experts highlighted various therapeutic options discussed in the event of relapse: EGFR inhibitors, various MDM2 inhibitors, and personalized combination therapies targeting both EGFR and CDK4/6. Additionally, the Molecular Tumor Board discussed the reported risk of resistance or hyper-progression with immune checkpoint blockade in the presence of EGFR and MDM2 alterations. Innovative approaches such as combining MDM2 and EGFR inhibitors with immunotherapy, as well as the use of teserpaturev, a genetically engineered herpes simplex virus were addressed. This case emphasizes the importance of personalized treatment strategies for GBM and the need for ongoing clinical research to explore novel therapeutic options.
Keywords: cancer; glioblastoma; molecular tumor board; precision oncology