Implementing patient derived organoids in functional precision medicine for patients with advanced colorectal cancer

Journal of Experimental & Clinical Cancer Research

Research

Isabelle Sourrouille¹  Mohamed-Amine Bani²  Peggy Dartigues²  Maxime Annereau³  Thierry De Baère⁴  Antoine Hollebecque⁵  Cristina Smolenschi⁵  Antoine Italiano⁶  Benjamin Besse⁷  Emilie Gontran⁸  Jacques R. R. Mathieu⁸  Jérôme Cartry⁸  Pierre Mathias⁸  Ali Mouawia⁸  Alice Boilève⁸  Sabrina Bedja⁸  Maximiliano Gelli⁹  Michel Ducreux^1,10  David Malka^1,11  Fanny Jaulin^1,12  Bastien Job^1,13 

[1] Département de Chirurgie Viscérale, Gustave Roussy, 94805, Villejuif, France;Département de Pathologie, Gustave Roussy, 94805, Villejuif, France;Département de Pharmacie Clinique, Gustave Roussy, 94805, Villejuif, France;Département de Radiologie Interventionnelle, Gustave Roussy, 94805, Villejuif, France;UFR Médecine, Université Paris-Saclay, 94270, Le Kremlin-Bicêtre, France;Département d’Innovation Thérapeutique et d’Essais Précoces, Gustave Roussy, 94805, Villejuif, France;Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France;Département d’Innovation Thérapeutique et d’Essais Précoces, Gustave Roussy, 94805, Villejuif, France;Gustave Roussy, Unité de Médecine de Précision, 94805, Villejuif, France;Gustave Roussy, Unité de Médecine de Précision, 94805, Villejuif, France;Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France;Inserm U-1279, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France;Inserm U-1279, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France;Département de Chirurgie Viscérale, Gustave Roussy, 94805, Villejuif, France;Inserm U-1279, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France;Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France;Inserm U-1279, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France;Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France;Département d’Oncologie Médicale, Institut Mutualiste Montsouris, Paris, France;Inserm U-1279, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France;Département de Recherche, Gustave Roussy, 94800, Villejuif, France;Inserm US23, Plateforme de Bioinformatique, Gustave Roussy, 94805, Villejuif, France;

关键词: Organoids;    Precision medicine;    Colorectal cancer;    Chemogram;   

DOI  :  10.1186/s13046-023-02853-4

 received in 2023-06-30, accepted in 2023-10-06,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundPatient Derived Organoids (PDOs) emerged as the best technology to develop ex vivo tumor avatars. Whether drug testing on PDOs to identify efficient therapies will bring clinical utility by improving patient survival remains unclear. To test this hypothesis in the frame of clinical trials, PDO technology faces three main challenges to be implemented in routine clinical practices: i) generating PDOs with a limited amount of tumor material; ii) testing a wide panel of anti-cancer drugs; and iii) obtaining results within a time frame compatible with patient disease management. We aimed to address these challenges in a prospective study in patients with colorectal cancer (CRC).MethodsFresh surgical or core needle biopsies were obtained from patients with CRC. PDOs were established and challenged with a panel of 25 FDA-approved anti-cancer drugs (chemotherapies and targeted therapies) to establish a scoring method (‘chemogram’) identifying in vitro responders. The results were analyzed at the scale of the cohort and individual patients when the follow-up data were available.ResultsA total of 25 PDOs were successfully established, harboring 94% concordance with the genomic profile of the tumor they were derived from. The take-on rate for PDOs derived from core needle biopsies was 61.5%. A chemogram was obtained with a 6-week median turnaround time (range, 4–10 weeks). At least one hit (mean 6.16) was identified for 92% of the PDOs. The number of hits was inversely correlated to disease metastatic dissemination and the number of lines of treatment the patient received. The chemograms were compared to clinical data obtained from 8 patients and proved to be predictive of their response with 75% sensitivity and specificity.ConclusionsWe show that PDO-based drug tests can be achieved in the frame of routine clinical practice. The chemogram could provide clinicians with a decision-making tool to tailor patient treatment. Thus, PDO-based functional precision oncology should now be tested in interventional trials assessing its clinical utility for patients who do not harbor activable genomic alterations or have developed resistance to standard of care treatments.

【 授权许可】

CC BY   
© Italian National Cancer Institute ‘Regina Elena’ 2023

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