Challenges in validation of combination treatment strategies for CRC using patient-derived organoids

Valentin Benboubker1,2,3, George M Ramzy1,2,3,4, Sacha Jacobs1,2,3

  • 1Molecular Pharmacology Group, School of Pharmaceutical Sciences, University of Geneva, 1 Rue Michel-Servet, Geneva, 4 1211, Switzerland.

Insights

Patient-derived organoids (PDOs) are valuable ex vivo models for cancer drug screening. This review explores their use in predicting combination therapy effectiveness and advancing personalized medicine in colorectal cancer (CRC).

Area of Science:

  • Oncology
  • Translational Medicine
  • Biotechnology

Background:

  • Patient-derived organoids (PDOs) are established ex vivo models derived from patient tumors.
  • PDOs exhibit phenotypic and genotypic similarity to the original tumor, complementing other cancer models.
  • The predictive potential of PDOs for combination therapy response is not fully understood.

Purpose of the Study:

  • To review the application of PDOs in validating and optimizing multi-drug combinations for personalized colorectal cancer (CRC) treatment.
  • To discuss advancements in creating more complex PDO models by incorporating diverse cell types.
  • To explore how advanced PDOs contribute to personalized medicine, especially in immunotherapy.

Main Methods:

  • Review of existing literature on patient-derived organoids in cancer research.
  • Analysis of recent advancements in PDO model development and cell type enrichment.
  • Discussion of PDO applications in combination therapy and immunotherapy for CRC.

Main Results:

  • PDOs show promise in screening and validating cancer drug candidates.
  • Enriching PDOs with diverse cell types improves their in vivo mimicry.
  • PDOs are increasingly used to predict sensitivity to combination therapies.

Conclusions:

  • Patient-derived organoids are crucial for advancing personalized medicine in CRC.
  • Sophisticated PDO models are narrowing the gap towards effective immunotherapy strategies.
  • Further research is needed to overcome challenges and fully realize the potential of PDOs.