Projects per year
Abstract
Zebrafish embryos are widely used for drug-discovery, however administering drugs to adult zebrafish is limited by current protocols that can cause stress. Here, we develop a drug formulation and administration method for adult zebrafish by producing food-based drug pellets which are consumed voluntarily. We apply this to zebrafish with BRAF-mutant melanoma, a model that has significantly advanced our understanding of melanoma progression, but not of drug resistance due to the limitations of current treatment methods. Zebrafish with melanomas responded to short-term, precise, and daily dosing with drug-pellets made with the BRAFV600E inhibitor, vemurafenib. On-target drug efficacy was determined by phospho-ERK staining. Continued drug treatment led to the emergence, for the first time in zebrafish, of acquired drug resistance and melanoma relapse, modelling the responses seen in melanoma patients. This
method presents a controlled, non-invasive approach that permits long-term drug studies, and can be widely applied to adult zebrafish models.
method presents a controlled, non-invasive approach that permits long-term drug studies, and can be widely applied to adult zebrafish models.
Original language | English |
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Journal | Disease Models and Mechanisms |
Early online date | 8 Apr 2022 |
DOIs | |
Publication status | E-pub ahead of print - 8 Apr 2022 |
Keywords / Materials (for Non-textual outputs)
- Adult zebrafish
- melanoma
- drug delivery
- long-term treatment
- drug resistance
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- 2 Finished
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Targeting persister cell states that drive drug resistance and metastasis
1/10/20 → 30/09/23
Project: Research
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