Questions to Dr Gwenaelle Gravis
How does the team of translational medicine in urology function?
The team combines clinicians of the urology department (oncologist, urologist, radiologist, radiation oncologist and pathologist), several research teams from CRCM (specialists in signaling pathways, immunology of cancer, oncogenetics ...), the head of the translational research team at IPC and common platform research teams of the Institute: integrated biology; medical imaging, including functional imaging; the biobank; the preclinical evaluation TrGET® platform, the unit dedicated to early clinical trials ETOH and of course the Department of Clinical Research and Innovation (DRCI).
Specifically, scientists have improved our understanding of disease and interpretation of clinical trials. In return, we provide biological samples and clinical data that enable them to confront their hypotheses with the reality of human pathology. Together, we also regularly evaluate the therapeutic potential of molecular targets discovered by researchers from CRCM or members of their network and the scientific rationale of new diagnostic or therapeutic developed by the biopharmaceutical industry.
What are your priority indications?
Logically where our patients need it most: metastatic kidney cancer and metastatic prostate cancer.
You have a reputation for being a "big recruiter," what types of clinical trials you prefer?
I'm actually very involved in clinical trials as an investigator or co-investigator because my first mission is to ensure that our patients benefit from the most up-to-date diagnostic and therapeutic advances. For this, we explore all clinical situations (neodjuvant, adjuvant, first line, relapse...) and all types of tests, from early clinical studies to post-marketing trials. The team is very well accustomed to the clinical evaluation of new therapies that enables us to guarantee the level of care and quality of process imposed by these tests notably early clinical studies.
A few years ago, the IPC was among the first institutes to evaluate the efficacy and safety of the anti-angiogenic Sunitinib/Sutent® (it prevents the production of blood vessels that supply the tumor), a drug that significantly improved the therapeutic management of patients with metastatic renal cell carcinoma. Since, in view of the side effects that we observe (bowel perforations, loss of teeth), we reported the results of a study on dental and gastrointestinal toxicity compared of sunitinib and chemotherapy at the 2011 congress of the ESMO (European Society for Medical Oncology).
For example, we recently launched two important clinical trials in metastatic prostate cancer:
The first is a Phase I/II study conducted in patients whose cancer already metastasized, is resistant to hormonal therapy (chemical castration with anti-androgenic drug). It aims to compare the effect of a treatment combining Docetaxel/Taxotere® (a chemotherapy) and Mazintinib (a novel inhibitor of tyrosine kinases) to treatment with this targeted drug combined with a different chemotherapy, Gemcitabine/Gemza®.
The second was a multicenter Phase III trial involving patients with metastatic hormone-sensitive prostate cancer (median survival of this group of patients is 5 years). This time we evaluated the benefits of additional chemotherapy with Docetaxel. We measured the response in both the tumor and serum (using tools such as proteomics and transcriptomics), while patients perform their own assessment (a methodology that is being generalized under the influence of the National Cancer Institute). In parallel, the Unit "Epidemiology and Social Sciences applied to medical innovation" of Jean-Paul Moatti evaluate the costs of this treatment and its impact on quality of life for patients. Presented at the last ASCO meeting, the first data from this ongoing study (365 patients over nearly 4 years) seems already to demonstrate that the treatment improves the clinical response: the Prostate-Specific- Antigen (PSA) increases more slowly in patients benefiting from this new combination therapy, which is very good sign!
Among the biological mechanisms explored by researchers from CRCM which ones especially affect your indications?
We lack biomarkers for the disease. From biological samples and data from our clinical trials, the team of Dr. Daniel Birnbaum attempts to identify molecular targets (defects in the expression of one or more genes) that could serve as prognostic markers in prostate cancer (In the United States, the team of Scott Tomlins at the University of Michigan has already identified a first candidate with the fusion gene TMPRSS2-ETS).
The PI3K/AKT signaling pathway is now a major therapeutic target in cancer (it plays a key role in cellular stability by affecting proliferation, differentiation and cell death). Dr. Jacques Nunes and his team have developed tools that allow us to evaluate the clinical action of new drugs that specifically target this pathway. The team of Pr Daniel Olive also explores the therapeutic potential of NK cells (Natural Killer) in association with us.
Finally, of course we're very interested in researches led by the team of Dr. Palma Rocchi that aim to restore the hormone sensitivity of prostate cancer.
L’équipe de médecine translationnelle en urologie
L’équipe associe les cliniciens du département d’urologie (oncologues, urologues, chirurgiens, radiologues, radiothérapeutes et anatomopathologistes), plusieurs équipes de recherche du CRCM (spécialistes des voies de signalisation, de l’immunologie des cancers, de l’oncogénétique) et les plateformes communes des équipes de recherche de l’Institut : la biologie intégrée, l’imagerie médicale, dont l’imagerie fonctionnelle, la tumorothèque, la plateforme d’évaluation préclinique TrGET®, l’unité dédiée aux essais cliniques précoces ETOH, la Direction de le Recherche Clinique et de l’Innovation (DRCI).
Doctors and researchers in this team
- Daniel BIRNBAUM
- Serge BRUNELLE (Doctor)
- Christian CHABANNON (Professor)
- Yves COLLETTE
- Valéria DE LUCA (Doctor)
- François EISINGER (Professor)
- Gwenaëlle GRAVIS-MESCAM (Doctor)
- Yoann KOSKAS (Doctor)
- Philippe MORTIER (Doctor)
- Catherine NOGUES (Doctor)
- Jacques NUNES
- Daniel OLIVE
- Christine PASERO
- Géraldine PIGNOT (Doctor)
- Palma ROCCHI
- Stanislas RYBIKOWSKI (Doctor)
- Naji SALEM (Doctor)
- Jean frederic SAUNIERE
- Hagay SOBOL (Professor)
- Sébastien TAIX (Doctor)
- Jeanne THOMASSIN-PIANA (Doctor)
- Jochen WALZ (Doctor)
- Luc XERRI (Professor)