Questions to Pr Norbert Vey
How does the research team in onco-hematology function?
It combines the clinical department of onco-hematology, hematology diagnostics specialists of the department of biopathology, several teams of researchers from the CRCM, four technology platforms (cytology, flow cytometry, conventional genetics and molecular biology) and of course, platforms common to the research teams of the Institute: the preclinical evaluation platform TrGET®, the immunomonitoring platform, the biobank and the unit dedicated to early clinical trials, ETOH.
Today, acute and chronic myeloid leukemia are both priority indications of the team.
In what areas of research are you working in particular?
Our research focuses in four areas:
1) Identify molecular abnormalities that lead to malignant transformation
This is the area of Daniel Birnbaum and his team. They try to decipher the molecular defects causing acute leukemias, myelodysplastic disorders and myeloproliferative disorders (chronic myeloid leukemia, polycythemia vera, essential thrombocythemia and myelofibrosis) to identify prognostic factors and new therapeutic targets. Recently, we have found that a gene mutation in ASXL1 (a gene involved in remodeling of chromatin, the basic substance of our chromosomes) was found in nearly 15% of myelodysplasia patients. That makes this mutation the second molecular defect identified in this area (the first is the tumor suppressor gene TET2). Now the objective is to assess the prognostic value of this biomarker and confirm the possible existence of a new subclass of myeloid malignancy.
2) Quantify and qualify the immune response of patients
Through the immunomonitoring platform of the Institute, the team of Daniel Olive evaluates the effect on the immune system of immunotherapies that we are testing in the clinic, such as anti-KIR antibody (a monoclonal antibody targeting natural killer (NK) cells) developed by Innate Pharma and Bristol-Myers Squibb from the work of one of our partners (the team of Professor Vivier, Centre d'Immunologie de Marseille-Luminy). We use this information to confirm the mechanism of drug action and reveal a possible correlation with the clinical responses we observe. In this case, the team also tested ex vivo other assumptions that have led to new clinical trials (in combination and in other indications).
3) Evaluate the field of epigenetics
The IPC is at the forefront of this emerging field that aims to correct defects in the regulation of genes frequently affecting cancer cells. Estelle Duprez's team is attempting to identify the molecules involved in these mechanisms and their impact on differentiation of normal and pathological blood cells. In turn, Yves Colette and his team explore the therapeutic component of this area. Besides their involvement in the interpretation of results of clinical trials of HDAC inhibitors (drugs that intervene in the often abnormal epigenetic regulation in cancer) and exploring how they work, they developed an original model of leukemia in mice, which now enables the team to test the effect of these new drugs in a situation closely approximating the clinical situation.
4) Challenge one major cell signaling pathway
There are many pathways that transport and convert information to the inside of our cells. The channel called PI3K/AKT plays a key role in cellular stability by contributing simultaneously to proliferation, differentiation and cell death. This signaling pathway is frequently deregulated in cancer, which is why researchers have developed new drugs that act directly on it. Jacques Nunes and his team have developed tools that allow us to evaluate the clinical activity of these molecules (termed anti-AKT) before, during and after treatment.
How and by what criteria are your clinical trials organized?
Our activity is highly diversified. We conduct both early clinical trials referred to as proof of concept clinical studies and more advanced (phase 2b and 3 trials, and post AMM studies, those performed after the release of the drug).
Our goal is to ensure that our patients have access as soon as possible to innovative compounds from our laboratories, or those of our partners in the biopharmaceutical industry. That is why we now focus on early trials.
Not only the activity of the department of oncology and hematology allows us to carry out such studies, but also with ETOH we have a tool that allows us to guarantee the level of care and quality imposed by this type of trial.
L’équipe de médecine translationnelle en hématologie
L’équipe associe les cliniciens du département d’onco-hématologie, les spécialistes du diagnostic hématologique du département de bio-pathologie, plusieurs équipes de chercheurs du CRCM, quatre plateformes technologiques (cytologie, cytométrie de flux, génétique conventionnelle et biologie moléculaire), ainsi que la plateforme d’évaluation préclinique TrGET®, d’immunomonitoring, la tumorothèque et l’unité dédiée aux essais cliniques précoces ETOH.
Chercheurs (chefs d’équipe CRCM)
- Michel Aurrand-Lions
- Daniel Birnbaum
- Jean Paul Borg
- Yves Collette
- Patrice Dubreuil
- Estelle Duprez
- Daniel Olive
L’unité ETOH : évaluer des approches thérapeutiques innovantes
Co-dirigée par les Pr Norbert Vey et Anthony Gonçalves, l’unité Evaluation Thérapeutique-Onco-Hématologie (ETOH) est un centre d’essais cliniques consacré aux phases précoces. Unique plateforme d’évaluation de nouvelles molécules labellisée par l’INCa pour la région PACA, l’unité ETOH dynamise le transfert vers la clinique des découvertes des équipes du CRCM ou de partenaires industriels.