Imipridones inhibit tumor growth and improve survival in an orthotopic liver metastasis mouse model of human uveal melanoma.
| العنوان: | Imipridones inhibit tumor growth and improve survival in an orthotopic liver metastasis mouse model of human uveal melanoma. |
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| المؤلفون: | Chattopadhyay C, Roszik J, Bhattacharya R, Alauddin M, Mahmud I, Yadugiri S, Ali MM, Khan FS, Prabhu VV, Lorenzi P, Burton E, Morey RR, Lazcano R, Davies MA, Patel SP, Grimm EA |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Jan 15. Date of Electronic Publication: 2024 Jan 15. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Purpose: Uveal melanoma (UM) is a highly aggressive disease with very few treatment options. We previously demonstrated that mUM is characterized by high oxidative phosphorylation (OXPHOS). Here we tested the anti-tumor, signaling and metabolic effects of imipridones, CLPP activators which reduce OXPHOS indirectly and have demonstrated safety in patients. Experimental Design: We assessed CLPP expression in UM patient samples. We tested the effects of imipridones (ONC201, ONC212) on the growth, survival, signaling and metabolism of UM cell lines in vitro, and for therapeutic effects in vivo in UM liver metastasis models. Results: CLPP expression was confirmed in primary and mUM patient samples. ONC201/212 treatment of UM cell lines in vitro decreased OXPHOS effectors, inhibited cell growth and migration, and induced apoptosis. ONC212 increased metabolic stress and apoptotic pathways, inhibited amino acid metabolism, and induced cell death-related lipids. ONC212 also decreased tumor burden and increased survival in vivo in two UM liver metastasis models. Conclusion: Imipridones are a promising strategy for further testing and development in mUM. |
| تواريخ الأحداث: | Date Created: 20240131 Latest Revision: 20240131 |
| رمز التحديث: | 20240131 |
| مُعرف محوري في PubMed: | PMC10827043 |
| DOI: | 10.1101/2024.01.12.575058 |
| PMID: | 38293232 |
| قاعدة البيانات: | MEDLINE |
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