PUBLICATION

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

Authors
Lu, Y., Patton, E.E.
ID
ZDB-PUB-220409-11
Date
2022
Source
Disease models & mechanisms   15(5): (Journal)
Registered Authors
Patton, E. Elizabeth
Keywords
Adult zebrafish, Drug delivery, Drug resistance, Long-term treatment, Melanoma, Vemurafenib
MeSH Terms
  • Animals
  • Cell Line, Tumor
  • Drug Implants/therapeutic use
  • Drug Resistance, Neoplasm
  • Humans
  • Indoles/pharmacology
  • Melanoma*/drug therapy
  • Mutation/genetics
  • Neoplasm Recurrence, Local/drug therapy
  • Pharmaceutical Preparations
  • Protein Kinase Inhibitors/pharmacology
  • Proto-Oncogene Proteins B-raf/genetics
  • Sulfonamides/pharmacology
  • Sulfonamides/therapeutic use
  • Zebrafish*
PubMed
35394030 Full text @ Dis. Model. Mech.
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.
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