Long-term non-invasive drug treatments in adult zebrafish that lead to melanoma drug resistance

Yuting Lu, E Elizabeth Patton*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
JournalDisease Models and Mechanisms
Early online date8 Apr 2022
Publication statusE-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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