Cancer: The tumour organoids steering treatment

Innovation Article published on 25 March 2022 , Updated on 25 March 2022

How can we be sure that the anti-cancer treatment given to a patient is the most suitable one to fight their cancer? By bringing together cell biology, statistics, and personalised medicine, the ORGANOMIC project aims to develop laboratory avatars of patient tumours on which different cancer therapies can be tested in advance. The most effective therapy in vitro should be the most promising for the patient. 

“Every tumour is unique. How it responds to treatment will be unique as well,” sets out Fanny Jaulin, researcher at the Tumour cell dynamics (DCT – Univ. Paris-Saclay, Gustave Roussy and Inserm) research unit and scientific and technical head of the ORGANOMIC project. Identifying which treatment should be used on a patient to get the best results against their cancer is a challenge for doctors. With the ORGANOMIC project, a winner of the recherche hospitalo-universitaire (university-hospital research, RHU) in Health call for proposals 2021 – which fosters partnerships between academic and industrial players with the aim of developing innovative treatments –, Fanny Jaulin and her team would like to improve this process using tumour organoids. These small-scale laboratory recreations patient tumours are used to perfect anti-cancer treatments.

Before the start of the project, the researcher and her team first optimised the method used to create these laboratory avatars. This method involves culturing around a hundred cancerous cells taken, via biopsy, from a patient’s tumour and putting them in a hydrogel, where they will create small balls. These spheres, which are a hundredth of a micrometre (0.1 mm) in diameter, are then subjected to a set of chemotherapy and immunotherapy tests, all while being examined under a microscope and analysed using molecular biology techniques to assess how they respond to the treatment. After proving that these avatars are indeed true copies of the patient’s tumour, the team also succeeded in demonstrating that their reaction mimics that of the patient in the same way. 

Today, the team wants to know if the information they have gathered can help doctors. “Are these good tools to guide a patient’s treatment? This is what is at stake in the clinical trials that are underway. We know that these tumour avatars work. We must now prove that they’re useful,” explains Fanny Jaulin. There would be a definite advantage to using these avatars. While doctors and pharmacists only have one try to identify a therapeutic strategy, with tumour organoids, biologists have more freedom to test possible treatment combinations.

 

Oncology turns to personalised medicine

Since the 1960s, anti-cancer treatments have become more accurate and take into account the diversity found among tumours. At first, doctors chose treatments according to the organ affected by the tumour, such as medicine from the taxane class for breast cancers. Progress in genetics allowed each tumour to be typified on a molecular scale. Fanny Jaulin explains: “These past few years, oncology has turned to personalised medicine. The most used approach at first was genomics, to predict treatments based on mutations. This, however, isn’t always effective, and only 7% of patients have access to it. We, therefore, want to propose an alternative approach based on observations, not predictions.” To do this, the team has developed fast, reliable, and standardised tests that can be used on cells taken from each patient. It is working on improving the miniaturisation of these tests using microfluidics. This will increase the number of tests that can be carried out with the same amount of the tumour sample.

“In time, our approach could be applied to all types of cancer. For our study, however, we made our observational field smaller and chose to test on gastrointestinal cancers. For colorectal cancers, which do not really respond treatments (less than 5% for immunotherapy) and are the second cause of death due to cancer, this could be revolutionary. This is even more important as this field is suffering from a lack of therapeutic innovation,” mentions Fanny Jaulin. It is with this goal in mind that the biologist works closely with doctors from the Digestive Diseases Committee at the Institut Gustave Roussy. In January 2022, phases I/II of the Organotreat clinical study were launched. The protocol developed by the team can now provide treatment recommendations for gastrointestinal treatments in less than two months.

 

A diagnosis in three acts

The clinical trial and research that have been carried out are now being continued within the ORGANOMIC project, which has three research axes. The first axis, CHEMOGRAM, directly continues the work of the Organotreat trial and aims to use tumour organoids to predict cancer’s response to chemotherapy. “Being able to test around twenty medicines on these avatars allows us to divert from traditional gastrointestinal tumour treatments, and to open analysis to anti-cancer medicines that are more commonly used for other types of cancer (breast cancer, pancreatic cancer, etc.). We can therefore test effective medicines that have already been authorised for the market but would not necessarily be a doctor’s first choice,” points out the researcher. Thanks to CHEMOGRAM, doctors will have an overview of medicines, including unusual ones, which have most effectively destroyed tumour cells in vitro, and can use this overview when prescribing treatments.

Following initial positive results, these researchers are already working on developing the next generation of tests. The second axis, IMMUNOGRAM, aims to predict the patient’s immune response to immunotherapy. This therapeutic strategy stimulates the immune system to help it destroy the tumour. The tumour organoids study poses a further challenge as it involves recreating what surrounds the tumour, including immune cells, not just cancerous cells.

The research undertaken as part of the project’s CHEMOGRAM and IMMUNOGRAM axes involves patients being treated for resistant cancer and whose illness is in its last line of therapy. Research should not interfere with patient care, which often initially requires other options such as surgery.

The last axis, INVAGRAM, concerns patients at the beginning of their illness. It involves observing how the tumour evolves over several years, as soon as it is detected. Alongside this, the team will examine the evolution of avatars that have been put in an environment that mimics tumour stroma. Thanks to the techniques developed by the team, it will be possible to monitor invasive dynamics in vitro and to see if certain tumour sphere behaviours (fast or slow invasion, collective or individual invasion, etc.) are related to the invasive ability of the tumour in the patient. If there is a link, it will be used to predict how dangerous the tumour is from the first stages of the illness.

 

A long-term project

ORGANOMIC, which has been funded for five years, includes several partners, such as Université Paris-Saclay (a founding member of the project), Inserm and Institut Gustave Roussy where the Organotreat clinical trial is taking place. Institut Pasteur and Okomera, a start-up, are also involved in developing microfluidic chips that are required to culture tumour organoids. CentraleSupélec will carry out imaging, IT, and statistical analyses. SEngine, a start-up that specialises in precision medicine, is also taking part in the project. AstraZeneca is involved in the development of tumour avatars.

The team hopes to have the first results shortly, as soon as analysis on phases I/II of the Organotreat clinical study has finished. In order to prove that these tumour avatars are useful, these scientists need to quickly collect as much data as possible from a limited sample of cells. They need to be able to prove the pertinence of these systematic tests in vitro to be able to steer doctors' decisions. “With our observational study, we hope that we can develop a pragmatic and comprehensive approach, and improve patient treatment,” concludes Fanny Jaulin.

 

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