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Updated: Jan 3, 2026
High-Throughput In Vitro Assay using Patient-Derived Tumor Organoids
Published on: June 14, 2021
Plocabulin Displays Strong Cytotoxic Activity in a Personalized Colon Cancer Patient-Derived 3D Organoid Assay
Alba Costales-Carrera1,2, Asunción Fernández-Barral1,2, Pilar Bustamante-Madrid1,2
1Department of Cancer Biology, Instituto de Investigaciones Biomédicas "Alberto Sols" (CSIC-UAM) 28029 Madrid, Spain and University Hospital La Paz Institute for Health Research (IdiPAZ), 28046 Madrid, Spain.
Abstract:
Plocabulin is a novel microtubule-disrupting antitumor agent of marine origin that is currently undergoing phase II clinical trials. Plocabulin has potent antiproliferative and antiangiogenic actions in carcinoma cell lines and has antitumor activity in xenografted mice. Here, we used three-dimensional (3D) tumor organoids derived from three colorectal cancer (CRC) patients to study the effect of plocabulin in a personalized assay system that ensures dose dependence and high reproducibility. The cytotoxicity of plocabulin was an order of magnitude higher than that of the active irinotecan derivative SN38 (7-ethyl-10-hydroxy-camptothecin) in tumor organoids at different passages. Moreover, plocabulin maintained its strong cytotoxic activity in wash-out experiments, in which a short pulse treatment of tumor organoids was as efficient as continuous treatment. Our data show that plocabulin has a very potent cytotoxic action in CRC patient-derived tumor organoids, supporting ongoing clinical trials with plocabulin and the use of organoid assays to provide personalized validation of antitumor drugs.
Insights
Plocabulin, a marine-derived antitumor drug, shows potent cytotoxicity against colorectal cancer (CRC) patient organoids. This novel agent is highly effective even with short exposure, supporting its clinical trials.
Area of Science:
- Oncology
- Marine Pharmacology
- Cancer Biology
Background:
- Plocabulin is a novel marine-derived microtubule-disrupting agent with demonstrated antiproliferative and antiangiogenic effects.
- Preclinical studies in carcinoma cell lines and xenografted mice indicate plocabulin's antitumor potential.
- Colorectal cancer (CRC) remains a significant health concern, necessitating novel therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy of plocabulin in a personalized three-dimensional (3D) tumor organoid system derived from CRC patients.
- To compare the cytotoxic activity of plocabulin with SN38, an active metabolite of irinotecan.
- To assess the impact of treatment duration on plocabulin's effectiveness using wash-out experiments.
Main Methods:
- Generation of 3D tumor organoids from three individual colorectal cancer (CRC) patients.
- Treatment of organoids with plocabulin and SN38 to assess cytotoxicity.
- Conducting wash-out experiments to evaluate the effect of short-pulsed plocabulin treatment.
- Utilizing patient-derived organoids for personalized drug response assessment.
Main Results:
- Plocabulin exhibited cytotoxicity an order of magnitude higher than SN38 in CRC patient-derived tumor organoids.
- The potent cytotoxic activity of plocabulin was maintained even after short pulse treatments in wash-out experiments.
- Plocabulin demonstrated dose-dependent and highly reproducible effects in the organoid assay system across different passages.
Conclusions:
- Plocabulin displays significant cytotoxic potency against colorectal cancer (CRC) patient-derived tumor organoids.
- The effectiveness of plocabulin in short-term exposure supports its therapeutic potential.
- Tumor organoid assays offer a valuable platform for personalized validation of novel antitumor drugs like plocabulin, supporting ongoing clinical trials.
