Patient-derived zebrafish xenograft models reveal ferroptosis as a fatal and druggable weakness in metastatic uveal melanoma
Groenewoud, A.; Yin, J.; Gelmi, M. C.; Alsafadi, S.; Nemati, F.; Decaudin, D.; Roman-Roman, S.; Kalirai, H.; Coupland, S. E.; Jochemsen, A. G.; Jager, M. J.; Snaar-Jagalska, E.
Show abstract
Uveal melanoma (UM) is the most common intraocular melanoma, derived from transformed melanocytes of the uvea. Although treatment of primary UM is usually successful, there is a high risk (up to 50%) of liver metastasis with negligible long-term survival. There are currently no reproducible patient-derived animal models that faithfully recapitulate the latter stages of metastatic dissemination of UM, hindering the discovery of curative treatments. To overcome this problem and to accelerate the development of new metastatic UM treatments, we developed a patient-derived zebrafish xenograft (zf-PDX) model, using spheroid cultures generated from metastatic and primary UM tissues. Engrafted UM cells derived from these spheroid cultures give rise to metastatic lesions and recapitulate the molecular features of UMs and their potential drug sensitivity. Importantly, harnessing this versatile model, we reveal a high sensitivity of circulating UM cells to ferroptosis induction in vivo by Erastin and RSL3. Our findings are further corroborated by supportive analysis of patient data implicating ferroptosis as a new, and druggable, target for the treatment of metastatic UM patients, specifically in those with BAP1 loss in the tumor.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A suspension technique for efficient large-scale cancer organoid culturing and perturbation screens 95%
- Long-term maintenance of patient-specific characteristics in tumoroids from six cancer indications in a common base culture media system 94%
- Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A 94%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- The RNA binding proteins LARP4A and LARP4B promote sarcoma and carcinoma growth and metastasis 94%
- A Non-genetic Mechanism for Chemoresistance in Lung Cancer: The Role of Integrin β4/Paxillin Axis 94%
- Versatile roles of Annexin A4 in ccRCC: impact on membrane repair, transcriptional signatures, and composition of the tumor microenvironment 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.