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Updated: Jun 12, 2025

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
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The landscape of drug sensitivity and resistance in sarcoma

Ahmad Al Shihabi1, Peyton J Tebon2, Huyen Thi Lam Nguyen3

  • 1Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Cell Stem Cell
|September 21, 2024
PubMed

Insights

Patient-derived tumor organoids (PDTOs) effectively predict sarcoma drug responses. This approach identified effective treatments for 59% of patients, paving the way for personalized sarcoma therapy.

Area of Science:

  • Oncology
  • Translational Medicine
  • Genomics

Background:

  • Sarcomas are rare cancers with over 100 subtypes, presenting therapeutic challenges due to heterogeneity and varied responses to approved regimens.
  • Personalized medicine approaches are crucial for improving outcomes in sarcoma patients.

Purpose of the Study:

  • To utilize patient-derived tumor organoids (PDTOs) for comprehensive drug sensitivity and resistance profiling in diverse sarcoma subtypes.
  • To establish a high-throughput screening pipeline for rapid assessment of therapeutic agents in sarcoma.

Main Methods:

  • Collected 194 sarcoma specimens from 126 patients across 24 subtypes for PDTO generation.
  • Employed a high-throughput organoid screening pipeline to test single agents and drug combinations.
  • Results were generated within one week of surgical specimen collection.

Main Results:

  • Drug sensitivity in PDTOs correlated with patient clinical features, including tumor subtype, treatment history, and disease progression.
  • The PDTO screening pipeline successfully identified at least one effective FDA-approved or NCCN-recommended regimen for 59% of tested specimens.
  • Organoid screening results showed potential to mirror individual patient outcomes.

Conclusions:

  • Patient-derived tumor organoids serve as a valuable preclinical model for predicting sarcoma drug response.
  • PDTO-based drug screening can provide actionable insights for personalized treatment selection in sarcoma.
  • This platform demonstrates significant potential to guide therapy and improve outcomes for sarcoma patients.
Keywords:
high-throughput drug screeningorganoidspatient-derived modelsprecision medicinesarcomatumor organoids

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