Organoids as preclinical models to improve intraperitoneal chemotherapy effectiveness for colorectal cancer patients with peritoneal metastases: Preclinical models to improve HIPEC

P. Roy, C. Canet-Jourdan, M. Annereau, O. Zajac, M. Gelli, S. Broutin, L. Mercier, A. Paci, F. Lemare, M. Ducreux, D. Elias, D. Malka, V. Boige, D. Goéré, F. Jaulin

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Background Peritoneal metastases (PM), corresponding to tumor implants into the peritoneal cavity, are associated with impaired prognosis and low responsiveness to systemic chemotherapy. A new therapeutic approach has dramatically changed the prognosis of patients with PM from colorectal cancer (CRC), consisting in the association of a complete cytoreductive surgery followed by intraperitoneal chemotherapy associated to hyperthermia (HIPEC). Many drugs have been administered intraperitoneally, but no clear consensus has been approved. Therefore, relevant preclinical models are essentials for the efficient translation of treatments option into affected patients. Method Organoids, the last generation of preclinical models, were used to rationalize and improve intraperitoneal chemotherapy. We tested several cytotoxics, combination, effect of hyperthermia, exposure duration and frequency. Results Organoids were a representative model of response to chemotherapies used for the treatment of PM from CRC; 460 mg/m2 of oxaliplatin being the most efficient cytotoxic treatment. Repeated incubations with oxaliplatin; mimicking cycles of intraperitoneal treatment, resulted in an increased efficacy. Conclusion & discussion Organoids are relevant models to study the chemosensitivity of peritoneal metastases from CRCs. These models could be used for large scale drug screening strategies or personalized medicine, for colorectal carcinoma but also for PM from other origins.

Original languageEnglish
Pages (from-to)143-152
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume531
Issue number1
DOIs
StatePublished - 5 Oct 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Elsevier B.V.

Funding

We thank the members of the Jaulin lab and Departments of Surgical and medical Oncology for discussion; Joel Raingeaud and Fotine Libanje for critical reading of the manuscript. This work was supported by the Gustave Roussy fund raising on colorectal cancer (Roulons pour le colon/mars bleu) and the ATIP-AVENIR program .

FundersFunder number
Wendy Will Case Cancer Fund
Association pour la Recherche sur le Cancer
Institut Gustave-Roussy

    Keywords

    • Colorectal carcinoma
    • HIPEC
    • Organoids
    • Peritoneal carcinomatosis
    • Preclinical

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