ZFIN ID: ZDB-PUB-191223-19
Developments in zebrafish avatars as radiotherapy sensitivity reporters - towards personalized medicine
Costa, B., Ferreira, S., Póvoa, V., Cardoso, M.J., Vieira, S., Stroom, J., Fidalgo, P., Rio-Tinto, R., Figueiredo, N., Parés, O., Greco, C., Ferreira, M.G., Fior, R.
Date: 2019
Source: EBioMedicine   51: 102578 (Journal)
Registered Authors: Ferreira, Miguel Godinho, Fior, Rita
Keywords: Chemoradiotherapy, Colorectal cancer, Personalized medicine, Radiotherapy, Zebrafish avatars
MeSH Terms:
  • Animals
  • Cell Line, Tumor
  • Chemoradiotherapy
  • Dose-Response Relationship, Radiation
  • Drug Resistance, Neoplasm/radiation effects
  • Genes, Reporter*
  • Humans
  • Precision Medicine*
  • Radiation, Ionizing
  • Rectal Neoplasms/radiotherapy*
  • Rectal Neoplasms/surgery
  • Xenograft Model Antitumor Assays
  • Zebrafish/physiology*
PubMed: 31862441 Full text @ EBioMedicine
ABSTRACT
Whereas the role of neoadjuvant radiotherapy in rectal cancer is well-established, the ability to discriminate between radioresistant and radiosensitive tumors before starting treatment is still a crucial unmet need. Here we aimed to develop an in vivo test to directly challenge living cancer cells to radiotherapy, using zebrafish xenografts.
We generated zebrafish xenografts using colorectal cancer cell lines and patient biopsies without in vitro passaging, and developed a fast radiotherapy protocol consisting of a single dose of 25 Gy. As readouts of the impact of radiotherapy we analyzed proliferation, apoptosis, tumor size and DNA damage.
By directly comparing isogenic cells that only differ in the KRASG13D allele, we show that it is possible to distinguish radiosensitive from radioresistant tumors in zebrafish xenografts, even in polyclonal tumors, in just 4 days. Most importantly, we performed proof-of-concept experiments using primary rectum biopsies, where clinical response to neoadjuvant chemoradiotherapy correlates with induction of apoptosis in their matching zebrafish Patient-Derived Xenografts-Avatars.
Our work opens the possibility to predict tumor responses to radiotherapy using the zebrafish Avatar model, sparing valuable therapeutic time and unnecessary toxicity.
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