20.500.12556/DiRROS-31849 Trametinib-mediated MEK inhibition impairs cancer cell viability and invasion in patient-derived tumor avatars of glioblastoma with extraneural metastases a proof-of-concept study Trametinib-mediated MEK inhibition impairs cancer cell viability and invasion in patient-derived tumor avatars of glioblastoma with extraneural metastases: a proof-of-concept study Glioblastoma (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. glioblastoma extraneural metastasis rare clinical case organoids MEK inhibitor cancer stem cells cell invasion glioblastom redek klinični primer MEK inhibitor rakave matične celice true false true Angleški jezik Slovenski jezik Neznano 2026-08-12 07:32:03 2026-08-12 07:32:04 2026-08-13 03:48:32 0000-00-00 00:00:00 2026 0 0 Nasl. z nasl. zaslona; Opis vira z dne 11. 8. 2026; str. 1-14 [article no.] ǂ119832 Vol. 202 Sept. 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 575.111 1950-6007 10.1016/j.biopha.2026.119832 287525635 RAZ_Novak_Metka_2026.pdf RAZ_Novak_Metka_2026.pdf 1 941145D91ED946EB19F4FFE4FB0E02D6 a0655187b8fdd7fb19549f89d8ae8fc67c97eb4ee008a68279b7fc38b23c8d6f 635d35ab-960f-11f1-af5a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=49489 https://doi.org/10.1016/j.biopha.2026.119832 1 2ae7c740-960f-11f1-af5a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=49488 Nacionalni inštitut za biologijo Univerzitetni klinični center Ljubljana 0 0 0