Related Experiment Video
Updated: Apr 14, 2026
Multiparametric Tumor Organoid Drug Screening Using Widefield Live-Cell Imaging for Bulk and Single-Organoid Analysis
Published on: December 23, 2022
A technology platform to assess multiple cancer agents simultaneously within a patient's tumor
Richard A Klinghoffer1, S Bahram Bahrami2, Beryl A Hatton1
1Presage Biosciences, Seattle, WA 98109, USA.
Abstract:
A fundamental problem in cancer drug development is that antitumor efficacy in preclinical cancer models does not translate faithfully to patient outcomes. Much of early cancer drug discovery is performed under in vitro conditions in cell-based models that poorly represent actual malignancies. To address this inconsistency, we have developed a technology platform called CIVO, which enables simultaneous assessment of up to eight drugs or drug combinations within a single solid tumor in vivo. The platform is currently designed for use in animal models of cancer and patients with superficial tumors but can be modified for investigation of deeper-seated malignancies. In xenograft lymphoma models, CIVO microinjection of well-characterized anticancer agents (vincristine, doxorubicin, mafosfamide, and prednisolone) induced spatially defined cellular changes around sites of drug exposure, specific to the known mechanisms of action of each drug. The observed localized responses predicted responses to systemically delivered drugs in animals. In pair-matched lymphoma models, CIVO correctly demonstrated tumor resistance to doxorubicin and vincristine and an unexpected enhanced sensitivity to mafosfamide in multidrug-resistant lymphomas compared with chemotherapy-naïve lymphomas. A CIVO-enabled in vivo screen of 97 approved oncology agents revealed a novel mTOR (mammalian target of rapamycin) pathway inhibitor that exhibits significantly increased tumor-killing activity in the drug-resistant setting compared with chemotherapy-naïve tumors. Finally, feasibility studies to assess the use of CIVO in human and canine patients demonstrated that microinjection of drugs is toxicity-sparing while inducing robust, easily tracked, drug-specific responses in autochthonous tumors, setting the stage for further application of this technology in clinical trials.
Insights
Cancer drug efficacy often fails in patients. The CIVO platform allows simultaneous in vivo testing of multiple drugs in solid tumors, improving preclinical cancer drug development and predicting patient outcomes.
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Preclinical cancer models poorly predict patient response to antitumor drugs.
- A significant challenge in cancer drug development is the poor translation of efficacy from preclinical models to patient outcomes.
Purpose of the Study:
- To introduce CIVO, a novel technology platform for simultaneous in vivo assessment of multiple anticancer drugs within a single solid tumor.
- To evaluate CIVO's ability to predict drug response and identify novel therapeutic strategies in preclinical cancer models and patient-derived tumors.
Main Methods:
- CIVO platform enables microinjection of up to eight drugs or drug combinations into solid tumors in animal models and patients.
- Validated CIVO in xenograft lymphoma models using known anticancer agents, assessing drug-specific cellular changes and predicting systemic drug response.
- Conducted an in vivo screen of 97 approved oncology agents using CIVO and assessed feasibility in human and canine patients.
Main Results:
- CIVO demonstrated spatially defined, drug-specific cellular changes in vivo, correlating with known drug mechanisms of action.
- Identified drug resistance to doxorubicin and vincristine, and enhanced sensitivity to mafosfamide in multidrug-resistant lymphomas.
- Discovered a novel mTOR pathway inhibitor with increased tumor-killing activity in drug-resistant settings and confirmed CIVO's toxicity-sparing and robust response induction in patient tumors.
Conclusions:
- CIVO accurately predicts in vivo drug responses and identifies novel therapeutic strategies, including resistance mechanisms and potential treatments for multidrug-resistant cancers.
- The CIVO platform shows promise for advancing cancer drug development by bridging the gap between preclinical efficacy and patient outcomes.
- Feasibility studies in human and canine patients indicate CIVO's potential for clinical application in toxicity-sparing drug response assessment.
