Method Profile

Multi-Lesion Colorectal Metastasis Organoid Drug-Response Comparison

Compare pharmacological heterogeneity among metastases from one patient against variation across patients.

Tumor ModelsOrganoids
Microplate reader with a multiwell plate.
Microplate reader with a multiwell plate. (Jean-Etienne Minh-Duy Poirrier, CC BY-SA 2.0)

Research Applications

Study the consequences of metastatic sampling and tumor phenotype for functional drug profiling.

Model & Design

213 organoids from colorectal liver metastases in 102 patients; multiple spatial lesions were represented for 65 patients.

Experimental Format

96-hour ATP-associated viability screens in two drug libraries, with matched molecular and histological characterization.

Model Components

  • Component

    Models

    Description

    Microsatellite-stable colorectal liver-metastasis organoids from a surgically treated cohort.

  • Component

    Drug libraries

    Description

    41- and 47-drug libraries with 24 shared drugs for principal cross-library comparisons.

  • Component

    Context

    Description

    Morphology, mutations, gene expression and available radiological treatment histories.

Measurements & Endpoints

  • Drug sensitivity scores
  • Pairwise within-patient and between-patient response distances
  • Morphological and molecular correlates

Analysis

Harmonize common drug ranges, compare model pairs at their stated sampling time and preserve the separation of lesion and patient denominators.

Published Evidence

  • Study Design

    Biobank-scale multi-lesion pharmacology and two selected treatment examples.

    Study Sample

    213 models from 102 patients; two prospective treatment decisions were described.

    Comparison

    Metastases within one patient versus models from different patients; cystic versus solid phenotypes.

    Finding

    Within-patient variation was lower overall but substantial in some patients; chemotherapy rechallenge and targeted therapy had different clinical outcomes.

    Interpretation & Limits
    • Culture success was associated with poorer prognosis and weaker preceding treatment response.
    • Established-model sensitivity did not reproduce the lesions’ preceding neoadjuvant response.
    • Two treatment examples do not establish cohort-wide predictive accuracy.

Sources

  1. Patient-derived organoids from metastatic colorectal cancer mirror tumor heterogeneity and predict patient survival and drug sensitivity. Cell Reports Medicine. First online 2026-05-28. ↗