Trametinib-mediated MEK inhibition impairs cancer cell viability and invasion in patient-derived tumor avatars of glioblastoma with extraneural metastasesNovak, Metka (Avtor) Majc, Bernarda (Avtor) Skoblar Vidmar, Marija (Avtor) Kladnik, Špela (Avtor) Kolenc Milavec, Tina (Avtor) Habič, Anamarija (Avtor) Galun, Simona Katrin (Avtor) Žižek, Pia (Avtor) Porčnik, Andrej (Avtor) Matjašič, Alenka (Avtor) Zupan, Andrej (Avtor) Jerala, Miha (Avtor) Bošnjak, Matic (Avtor) Prestor, Borut (Avtor) Breznik Vittori, Barbara (Avtor) glioblastomaextraneural metastasisrare clinical caseorganoidsMEK inhibitorcancer stem cellscell invasionGlioblastoma (GBM) remains one of the most lethal human malignancies, yet extraneural metastases are exceptionally rare and poorly understood. Standard treatment—surgical resection followed by chemoradiotherapy—offers only modest survival benefits, and therapeutic options for metastatic GBM are limited. Here, we describe a rare clinical case of metastatic GBM and provide comprehensive molecular characterization alongside a potential targeted treatment strategy. The tumor exhibited several molecular features associated with aggressive behavior, including alterations in the tumor suppressor genes NF1, TP53, PTEN, and RB1, a mesenchymal DNA‑methylation subclass, and activation of the MAPK signaling pathway. To functionally evaluate therapeutic vulnerabilities, we developed tumor models using patient‑derived GBM cells and their assembloids with cerebral organoids that recapitulate patient‑specific tumor biology and the human brain microenvironment. We identified the MEK inhibitor trametinib as a promising candidate capable of selectively reducing viability and invasion of highly aggressive, stem‑like GBM cells within our personalized patient-derived tumor avatars. This work highlights the proof-of-concept evidence that MEK pathway inhibition may represent a potential therapeutic vulnerability to counteract rapid tumor spread and improve responsiveness to temzolomide in this individual metastatic GBM case. Study underscores the need for continued research to advance targeted, multi‑modal therapeutic approaches for GBM.20262026-08-12 07:32:03Neznano31849sl