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Updated: Mar 22, 2026
Establishing 3-Dimensional Spheroids from Patient-Derived Tumor Samples and Evaluating their Sensitivity to Drugs
Published on: December 16, 2022
Phenotypic profiles for anticancer drug responses using tumor spheroids
Youngwon Kim1, Jiseok Lim2, Bongseop Kwak3
1College of Medicine, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyangsi, Gyeonggi-do 10326, Republic of Korea.
Abstract:
Phenotypic drug discovery enables the evaluation of anticancer drug responses without requiring prior knowledge of molecular targets. Tumor spheroids more accurately recapitulate in vivo tumor architecture compared to conventional monolayer cultures but currently lack standardized drug evaluation criteria. In this study, we fabricated uniform and drug evaluation-optimized tumor spheroids using triple-positive (ER+, PR+, HER2 +) invasive ductal carcinoma cells. Anticancer drugs used in breast cancer were administered at clinically relevant plasma concentrations. We propose drug response evaluation parameters including spheroid size change, morphological features (surface cell size and convexity), and optical transmittance monitored during drug treatment and throughout a defined post exposure observation period. These optical image-based analytical features showed consistent correlations with the respective mechanisms of molecular action and the associated drug response. This study establishes a phenotype-based evaluation system for breast cancer chemotherapy using tumor spheroids, offering a reference model for drug evaluation. Moreover, it proposes quantifiable evaluation parameters for drug screening and provides reference data for assessing investigational compounds, thereby enhancing the utility of spheroids in phenotypic anticancer drug discovery.
Insights
This study introduces a new method using tumor spheroids to test breast cancer drugs. It offers standardized criteria for evaluating drug effectiveness based on observable changes.
Area of Science:
- Oncology
- Drug Discovery
- Biotechnology
Background:
- Phenotypic drug discovery evaluates anticancer drug responses without target knowledge.
- Tumor spheroids mimic in vivo tumor architecture better than 2D cultures.
- Standardized drug evaluation criteria for spheroids are lacking.
Purpose of the Study:
- To develop a standardized, phenotype-based evaluation system for breast cancer chemotherapy using tumor spheroids.
- To establish quantifiable parameters for drug screening and evaluation.
- To enhance the utility of spheroids in phenotypic anticancer drug discovery.
Main Methods:
- Fabricated uniform tumor spheroids from triple-positive (ER+, PR+, HER2+) invasive ductal carcinoma cells.
- Administered breast cancer anticancer drugs at clinically relevant plasma concentrations.
- Proposed and monitored drug response evaluation parameters: spheroid size change, morphological features (surface cell size, convexity), and optical transmittance.
Main Results:
- Developed optical image-based analytical features for drug response evaluation.
- Demonstrated consistent correlations between analytical features, molecular mechanisms of action, and drug response.
- Validated the proposed parameters during drug treatment and post-exposure observation.
Conclusions:
- Established a phenotype-based evaluation system for breast cancer chemotherapy using tumor spheroids.
- Proposed quantifiable parameters for drug screening and evaluation.
- Provided a reference model and data for assessing investigational compounds in phenotypic drug discovery.
