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RHU Organomic: Organoids to Predict Treatment Response in Gastrointestinal Cancers
Organomic is one of four innovative, large-scale projects coordinated by Gustave Roussy. Led by Fanny Jaulin and her team, it was selected for funding as part of the fifth call for proposals under the University Hospital Health Research (RHU) initiative within the Investments for the Future program. It is based on the creation of organoids—or miniaturized 3D models—of a patient’s tumor to test a range of existing treatments. This key tool in personalized medicine offers a new treatment option for patients with metastatic gastrointestinal cancers.
University Hospital Research
Derived from stem cell technology, organoids are 3D biological replicas of a patient’s tumor created in the laboratory from a sample taken in the operating room. These models are capable of reproducing the specific characteristics (genetic, histological, morphological, etc.) of each tumor.
Fanny Jaulin’s team, which leads the ORGANOMIC project—a key component of Gustave Roussy’s 2030 strategy—aims to test a range of existing treatments for a given tumor using these organoids. Thanks to this innovative tool, it will now be possible to create a personalized treatment plan for each patient capable of predicting their response to a treatment, thereby better guiding them toward the treatment that proved most effective on the organoid.
The project consortium brings together clinical and academic research expertise from Gustave Roussy, Inserm, the Pasteur Institute, CentraleSupélec, Paris Saclay University, as well as two biotech companies, SEngine and Okomera, and a pharmaceutical company, AstraZeneca.
A personalized treatment for patients with metastatic colorectal cancer
Responsible for 17,000 deaths per year in France, colorectal cancers rank third among the most common types of cancer in both men and women. When diagnosed at a localized stage, they are easily treatable with surgery. But if they spread and become metastatic, chemotherapy remains the standard of care, as these cancers have unfortunately not benefited from two major advances in oncology: targeted therapies and immunotherapies.
To address this therapeutic impasse, the project is deploying a predictive diagnostic tool for treatments—including immunotherapies—to identify which treatments will be effective, direct patients to them as early as possible, and thereby maximize the chances of a cure. ORGANOMIC is divided into three subprograms.
To validate the clinical efficacy of a personalized chemotherapy regimen based on the patient’s tumor organoid. The goal is to standardize and automate this tool as early as the time of diagnosis. The prospective, multicenter ORGANOTREAT-01 trial is the very first in France to validate the efficacy and safety of these chemograms. More than 26 chemotherapy drugs and targeted therapies will be tested, either alone or in combination.
Similarly, the IMMUNOGRAMME platform will be used to predict the response to immune checkpoint inhibitors or to a combination of chemotherapy and immunotherapy in a patient-derived organoid containing immune cells—a first! The ORGANO PREDICT observational study will examine the response of patients’ tumor organoids to various immunotherapies for lung cancer in order to develop a personalized immunogram.
The INVAGRAMME diagnostic technology is intended to enable the assessment of tumor invasiveness at the time of diagnosis for patients who develop metastatic cancer. The goal of this device is to enable early prediction of a tumor’s aggressiveness and invasive potential using technology based on microfluidic processes.
Cutting-Edge Technologies and Ultra-Personalized Medicine
To develop organoids on a large scale in the laboratory at Gustave Roussy, Fanny Jaulin and her team use microscopic imaging and combine cutting-edge expertise in cellular biology, microfluidic chips, applied mathematics, and artificial intelligence.
The results of this research will lead to a dozen products marketed as in vitro diagnostic tests to enhance medical practice, as well as tools for research and development in oncology. These functional personalized medicine tests, developed by ORGANOMIC using patient-derived organoids, are also intended to be expanded to other types of cancer. They represent a true paradigm shift in understanding the complexity of cancer and treating patients.