Zebrafish Avatar-test forecasts clinical response to chemotherapy in patients with colorectal cancer

Nat Commun. 2024 Jun 5;15(1):4771. doi: 10.1038/s41467-024-49051-0.

Abstract

Cancer patients often undergo rounds of trial-and-error to find the most effective treatment because there is no test in the clinical practice for predicting therapy response. Here, we conduct a clinical study to validate the zebrafish patient-derived xenograft model (zAvatar) as a fast predictive platform for personalized treatment in colorectal cancer. zAvatars are generated with patient tumor cells, treated exactly with the same therapy as their corresponding patient and analyzed at single-cell resolution. By individually comparing the clinical responses of 55 patients with their zAvatar-test, we develop a decision tree model integrating tumor stage, zAvatar-apoptosis, and zAvatar-metastatic potential. This model accurately forecasts patient progression with 91% accuracy. Importantly, patients with a sensitive zAvatar-test exhibit longer progression-free survival compared to those with a resistant test. We propose the zAvatar-test as a rapid approach to guide clinical decisions, optimizing treatment options and improving the survival of cancer patients.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / pathology
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Precision Medicine / methods
  • Progression-Free Survival
  • Xenograft Model Antitumor Assays
  • Zebrafish*

Substances

  • Antineoplastic Agents