Questions to Dr Jean-Luc Raoul
What is the main goal of the Digestive translational research team?
The team is at the heart of the activities of one of the largest care units of the Institute, in terms of patients (we treat about 1400 patients each year) and physicians (the unit has five digestive surgeons, four gastroenterologists, three radiologists, two pathologists, a radiotherapist, a nuclear physician and three medical oncologists).
As clinicians, our first goal is to offer our patients the best treatment but also to ensure that they are part of a true therapeutic strategy. This requires us to use existing treatments as intelligently as possible, ie finding the right combination therapies. Then of course we must help develop new treatments that are more effective, safer and better adapted to the individual patient profile. The team contributes to these objectives by bringing together clinicians from the unit and basic researchers from CRCM. We enrich their research with our observations, biological samples and data from our tests, they shed light on the biology of the disease and help to interpret the results of our studies and together we evaluate new therapeutic opportunities from their laboratories or those of the biopharmaceutical industry.
To carry out this work we have a favorable biotope: the scientific and medical expertise of a very high level, a variety of models and scales of analysis and tools, such as the unit dedicated to early clinical trials ETOH and the Department of Clinical Research and Innovation (DRCI), which enable us to guarantee the level of care and quality that our clinical trials impose.
In digestive cancers, what is the impact of this new personalized medicine?
It is already at work in some of of diseases we follow. To date, the best known example is the K-RAS gene in colorectal cancers. Today, when the gene responsible for the proliferation and growth of tumor cells is not mutated, patients whose cancer has already metastasized, can receive treatment with Cetuximab/Erbitux® or Panitumumab/Vectibix® (monoclonal antibodies that prevent tumor cells from receiving the signal that promotes their proliferation and their division by blocking EGF receptor).
Other indications also benefit from these advances. Thus, by inhibiting the action of an enzyme directly involved in the disease (tyrosine kinase c-Kit), Imatinib/Glivec® has revolutionized the treatment of gastrointestinal stromal tumors. The monoclonal antibody Trastuzumab/Herceptin® also improved the prognosis of patients with stomach or esophageal cancer HER2+ (cancer cells of nearly 15% of patients have large numbers of HER2 receptors on their surface that contribute to their growth and multiplication).
Personalized medicine is the future but it is also a future of great complexity
Still, unlike blood cancers, digestive cancers are very complex and multifactorial diseases. These tumors have multiple genetic alterations leading to overactivation or inactivation of many genes. The result is, for example in colon cancer, if we now know the target molecule of Bevacizumab/Avastin®, we do know in advance for which patients the medicine will work. Even the extraordinary saga – EGF receptor, anti-EGF receptor monoclonal antibodies (Cetuximab, Panitumumab) - has limitations. First, surprisingly treatment with Cetuximab or Panitumumab do not work on patients (nearly 40%) whose cancer cells have a mutation of K-RAS gene, whereas the function of this gene seems rather far from the mechanism of action of drug. The latter is based on the blockage of EGF receptor and paradoxically the product works that the latter is present or not on the surface of tumor cells.
The other surprise is the tolerance problems we sometimes face. Treatments combining Cetuximab and Bevacizumab (this anti-angiogenic drug blocks the production of vessels supplying the tumor) are not well tolerated by patients while each drug targets a different signaling pathway. Where it was expected logically that 1 + 1 = 2 or 3, the result was therefore not even 2.
Personalized medicine is the future but also a future of great complexity. Today, these results make us humble about the disease but they also open up new avenues of research that scientists and clinicians from CRCM and IPC began to explore.
What are these new fields of research?
Researchers at the CRCM are trying to understand the complex genetic mechanics and update theranostic markers (markers for diagnosis and therapy) that we are sorely lacking. They also explore the relationship between tumor and its environment. This is a key issue because the stroma controls many aspects of the tumor. The team of Dr. Juan Iovanna is trying to understand how pancreatic cancer cells manage to survive in the hostile environment around them (little or no oxygen, nutrients...). This work could lead to new therapeutic targets capable of lowering the stress response of these tumors.
On our side we also work with many other teams to initiate new therapeutic opportunities.
Exactly what types of clinical trials do you prefer?
What interests us is to put our fingers on new molecules, to test new patterns, new combination therapies ... For that we intend to explore all clinical situations and all types of tests, from early clinical studies, the field of Dr. Antony Gonçalves, to post-marketing trials. In this area, the IPC has medical expertise, science and technology of a very high level but also a real expertise in terms of quality, staff and logistics.
L’équipe de médecine translationnelle dédiée aux cancers digestifs
Doctors and researchers in this team
- Erwan BORIES (Doctor)
- Fabrice CAILLOL (Doctor)
- Cécile DE CHAISEMARTIN (Doctor)
- Jean-Robert DELPERO (Professor)
- Slimane DERMECHE (Doctor)
- Nelson DUSETTI
- Jacques EWALD (Doctor)
- Catherine FAUCHER-BARBEY (Doctor)
- Marine GILABERT (Doctor)
- Marc GIOVANNINI (Doctor)
- Anthony GONÇALVES (Professor)
- Jérôme GUIRAMAND (Doctor)
- Juan IOVANNA
- Bernard LELONG (Doctor)
- Emilie MAMESSIER
- Hélène MEILLAT (Doctor)
- Laurence MOUREAU-ZABOTTO (Doctor)
- Christian PESENTI (Doctor)
- Flora POIZAT (Doctor)
- Genevieve RANCHIN/MONGES
- Jean-Philippe RATONE (Doctor)
- Pauline RIES (Doctor)
- Jean frederic SAUNIERE
- Olivier TURRINI (Doctor)
Cancer du pancréas : identifier les mécanismes de sensibilité aux chimiothérapies grâce à la biologie moléculaire
A partir des résultats issus du projet PACAomics, les cliniciens de l’IPC vont collaborer avec l’équipe du CRCM sur un grand projet clinique qui démarre en Janvier 2018.
Ce projet, appelé Oncosnipe, vise à développer de manière plus approfondie, via des prélèvements tumoraux effectués chez les patients atteints d’un cancer du pancréas, les approches d’examens moléculaires (génomique, protéomique) pour identifier quel patient sera sensible à quelle chimiothérapie.
Il s’agit d’un essai particulièrement innovant qui pourrait nous amener à court terme à traiter les patients de la façon la plus proche possible d’une médecine personnalisée.