Adding New Dimensions to 3D Cancer Models

Kevan Chu1,2, Lukas E Dow1,2,3,4

  • 1Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.

Cancer Research
|February 9, 2024
PubMed

Insights

This study reveals how the tumor microenvironment (TME) impacts cancer drug response. Patient-derived organoids and a new algorithm show TME factors influence chemotherapy effectiveness and drug resistance.

Area of Science:

  • Oncology
  • Cancer Biology
  • Immunology

Background:

  • Understanding patient-specific responses to anticancer therapies is crucial.
  • The tumor microenvironment (TME) significantly influences treatment efficacy.
  • Interactions between tumor cells and their microenvironment remain complex.

Purpose of the Study:

  • To investigate the impact of the TME on diverse anticancer treatments.
  • To develop a method for analyzing complex, multidimensional treatment response data.
  • To identify factors within the TME that affect chemotherapy response and drug resistance.

Main Methods:

  • Coupled patient-derived organoids (PDOs) and cancer-associated fibroblast (CAF) cocultures.
  • Employed high-throughput mass cytometry for cell state assessment.
  • Developed and utilized a novel "Trellis" algorithm for data integration and analysis.

Main Results:

  • Tumor cell response to chemotherapy is linked to intrinsic and non-intrinsic signaling.
  • Proliferative rate, growth factor signaling, and CAF interactions modulate chemoprotection.
  • The TME may promote lineage plasticity, contributing to drug resistance.

Conclusions:

  • The developed pipeline offers a framework for studying TME influences on cancer treatment.
  • This approach can elucidate the complex interplay of factors affecting therapeutic outcomes.
  • Findings highlight the TME's role in chemotherapy response and acquired drug resistance.