| Naslov: | 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 |
|---|
| Avtorji: | ID Novak, Metka (Avtor)
ID Majc, Bernarda (Avtor)
ID Skoblar Vidmar, Marija (Avtor)
ID Kladnik, Špela (Avtor)
ID Kolenc Milavec, Tina (Avtor)
ID Habič, Anamarija (Avtor)
ID Galun, Simona Katrin (Avtor)
ID Žižek, Pia (Avtor)
ID Porčnik, Andrej (Avtor)
ID Matjašič, Alenka (Avtor)
ID Zupan, Andrej (Avtor)
ID Jerala, Miha (Avtor)
ID Bošnjak, Matic (Avtor)
ID Prestor, Borut (Avtor)
ID Breznik Vittori, Barbara (Avtor) |
|---|
| Datoteke: |  PDF - Predstavitvena datoteka, prenos (9,93 MB)
MD5: 941145D91ED946EB19F4FFE4FB0E02D6
 URL - Izvorni URL, za dostop obiščite https://doi.org/10.1016/j.biopha.2026.119832
|
|---|
| Jezik: | Angleški jezik |
|---|
| Tipologija: | 1.01 - Izvirni znanstveni članek |
|---|
| Organizacija: |  NIB - Nacionalni inštitut za biologijo
 UKC LJ - Univerzitetni klinični center Ljubljana
|
|---|
| Povzetek: | 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. |
|---|
| Ključne besede: | glioblastoma, extraneural metastasis, rare clinical case, organoids, MEK inhibitor, cancer stem cells, cell invasion |
|---|
| Status publikacije: | Objavljeno |
|---|
| Verzija publikacije: | Objavljena publikacija |
|---|
| Leto izida: | 2026 |
|---|
| Št. strani: | str. 1-14 |
|---|
| Številčenje: | Vol. 202, [article no.] ǂ119832 |
|---|
| PID: | 20.500.12556/DiRROS-31849  |
|---|
| UDK: | 575.111 |
|---|
| ISSN pri članku: | 1950-6007 |
|---|
| DOI: | 10.1016/j.biopha.2026.119832 |
|---|
| COBISS.SI-ID: | 287525635 |
|---|
| Opomba: | Nasl. z nasl. zaslona;
Opis vira z dne 11. 8. 2026; |
|---|
| Datum objave v DiRROS: | 12.08.2026 |
|---|
| Število ogledov: | 147 |
|---|
| Število prenosov: | 82 |
|---|
| Metapodatki: |    |
|---|
|
:
|
Kopiraj citat |
|---|
| | | | Objavi na: |  |
|---|
Postavite miškin kazalec na naslov za izpis povzetka. Klik na naslov izpiše
podrobnosti ali sproži prenos. |
