Patient-derived organoids in gastric cancer: bridging the tumor microenvironment to functional precision oncology

Ji Ma1, Xinyang Liu2, Hongtao Xu1

  • 1Gastrointestinal Surgery Department, Lishui Municipal Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China.

Insights

Patient-derived cancer organoids (PDCOs) offer a 3D model to study gastric cancer (GC) and its microenvironment. These organoids show promise in predicting patient response to various therapies, advancing precision oncology.

Area of Science:

  • Oncology
  • Cancer Biology
  • Biotechnology

Background:

  • Gastric cancer (GC) presents a significant global health issue due to its molecular complexity and evolving tumor microenvironment (TME).
  • Genomic sequencing, while valuable for precision medicine, has limitations in fully capturing TME interactions and predicting patient treatment responses.
  • Patient-derived cancer organoids (PDCOs) are emerging as advanced 3D models that closely mimic the original tumor's characteristics.

Purpose of the Study:

  • To review the advancements in utilizing GC-PDCOs for simulating the TME and understanding immune evasion strategies.
  • To highlight the potential of PDCOs as patient avatars in functional precision oncology for predicting therapeutic outcomes.
  • To explore the integration of new technologies for overcoming translational challenges in organoid research.

Main Methods:

  • Systematic review of literature on gastric cancer patient-derived cancer organoids (GC-PDCOs).
  • Analysis of PDCO capabilities in recapitulating tumor histology, mutational profiles, and phenotypes.
  • Evaluation of PDCOs in modeling TME interactions and immune evasion mechanisms (camouflage, coercion, cytoprotection).

Main Results:

  • GC-PDCOs effectively replicate the histological and molecular features of parent tumors.
  • PDCOs demonstrate significant potential in predicting patient sensitivity to chemotherapy, targeted therapy, and immunotherapy.
  • Early studies show high clinical concordance between PDCO predictions and actual patient responses.

Conclusions:

  • PDCOs serve as high-fidelity models for studying GC and its TME, offering insights into immune evasion.
  • Organoid technology holds transformative potential for functional precision oncology, enabling personalized treatment strategies.
  • Integrating organoids with AI and 3D bioprinting can accelerate clinical translation for individualized gastric cancer therapy.

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