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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2024

Open Access 01-12-2024 | Colorectal Cancer | Research

Colorectal carcinoma peritoneal metastases-derived organoids: results and perspective of a model for tailoring hyperthermic intraperitoneal chemotherapy from bench-to-bedside

Authors: Luca Varinelli, Davide Battistessa, Marcello Guaglio, Susanna Zanutto, Oscar Illescas, Ewelina J. Lorenc, Federica Pisati, Shigeki Kusamura, Laura Cattaneo, Giovanna Sabella, Massimo Milione, Alessia Perbellini, Sara Noci, Cinzia Paolino, Elisabetta Khun, Margherita Galassi, Tommaso Cavalleri, Marcello Deraco, Manuela Gariboldi, Dario Baratti

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2024

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Abstract

Background

Peritoneal metastases from colorectal cancer (CRCPM) are related to poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been reported to improve survival, but peritoneal recurrence rates are still high and there is no consensus on the drug of choice for HIPEC. The aim of this study was to use patient derived organoids (PDO) to build a relevant CRCPM model to improve HIPEC efficacy in a comprehensive bench-to-bedside strategy.

Methods

Oxaliplatin (L-OHP), cisplatin (CDDP), mitomycin-c (MMC) and doxorubicin (DOX) were used to mimic HIPEC on twelve PDO lines derived from twelve CRCPM patients, using clinically relevant concentrations. After chemotherapeutic interventions, cell viability was assessed with a luminescent assay, and the obtained dose–response curves were used to determine the half-maximal inhibitory concentrations. Also, induction of apoptosis by different HIPEC interventions on PDOs was studied by evaluating CASPASE3 cleavage.

Results

Response to drug treatments varied considerably among PDOs. The two schemes with better response at clinically relevant concentrations included MMC alone or combined with CDDP. L-OHP showed relative efficacy only when administered at low concentrations over a long perfusion period. PDOs showed that the short course/high dose L-OHP scheme did not appear to be an effective choice for HIPEC in CRCPM. HIPEC administered under hyperthermia conditions enhanced the effect of chemotherapy drugs against cancer cells, affecting PDO viability and apoptosis. Finally, PDO co-cultured with cancer-associated fibroblast impacted HIPEC treatments by increasing PDO viability and reducing CASPASES activity.

Conclusions

Our study suggests that PDOs could be a reliable in vitro model to evaluate HIPEC schemes at individual-patient level and to develop more effective treatment strategies for CRCPM.
Appendix
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Metadata
Title
Colorectal carcinoma peritoneal metastases-derived organoids: results and perspective of a model for tailoring hyperthermic intraperitoneal chemotherapy from bench-to-bedside
Authors
Luca Varinelli
Davide Battistessa
Marcello Guaglio
Susanna Zanutto
Oscar Illescas
Ewelina J. Lorenc
Federica Pisati
Shigeki Kusamura
Laura Cattaneo
Giovanna Sabella
Massimo Milione
Alessia Perbellini
Sara Noci
Cinzia Paolino
Elisabetta Khun
Margherita Galassi
Tommaso Cavalleri
Marcello Deraco
Manuela Gariboldi
Dario Baratti
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2024
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-024-03052-5

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