AXL inhibition improves BRAF-targeted treatment in melanoma
Permanent lenke
https://hdl.handle.net/10037/26400Dato
2022Type
Journal articleTidsskriftartikkel
Peer reviewed
Forfatter
Nyakas, Marta Sølvi; Fleten, Karianne Giller; Haugen, Mads Haugland; Engedal, Nikolai; Sveen, Christina; Farstad, Inger Nina; Flørenes, Vivi Ann; Prasmickaite, Lina; Mælandsmo, Gunhild Mari; Vasiliauskaite, KotrynaSammendrag
More than half of metastatic melanoma patients receiving standard therapy fail to achieve a long-term
survival due to primary and/or acquired resistance. Tumor cell ability to switch from epithelial to a
more aggressive mesenchymal phenotype, attributed with AXLhigh molecular profle in melanoma, has
been recently linked to such event, limiting treatment efcacy. In the current study, we investigated
the therapeutic potential of the AXL inhibitor (AXLi) BGB324 alone or in combination with the
clinically relevant BRAF inhibitor (BRAFi) vemurafenib. Firstly, AXL was shown to be expressed in
majority of melanoma lymph node metastases. When treated ex vivo, the largest reduction in cell
viability was observed when the two drugs were combined. In addition, a therapeutic beneft of
adding AXLi to the BRAF-targeted therapy was observed in pre-clinical AXLhigh melanoma models
in vitro and in vivo. When searching for mechanistic insights, AXLi was found to potentiate BRAFiinduced apoptosis, stimulate ferroptosis and inhibit autophagy. Altogether, our fndings propose AXLi
as a promising treatment in combination with standard therapy to improve therapeutic outcome in
metastatic melanoma.
Forlag
Springer NatureSitering
Nyakas, Fleten, Haugen, Engedal, Sveen, Farstad, Flørenes, Prasmickaite, Mælandsmo, Vasiliauskaite. AXL inhibition improves BRAF-targeted treatment in melanoma. Scientific Reports. 2022;12(1):5076Metadata
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