The CRCM and IPC share the ambition to develop fundamental, translational and clinical research in a coordinated manner with the ultimate goals to identify biomarkers and therapeutic targets of clinical value.
Questions to Jean-Paul Borg, Director of the CRCM
What is the identity card of the CRCM “version 2012?”
The CRCM is an original center in the landscape of French research. This originality is not only due to its location in the heart of the Institut Paoli-Calmettes but also to his vocation: to advance the biology and medicine of cancer while working at the physiological and pathological interface, the fundamental and the applied, research and the clinic. This continuum between basic research, translational research and clinical research is really the hallmark of the CRCM. As an example, most of our publications are co-authored by scientists and clinicians, which is far from the norm in our discipline!
Understand, diagnose and treat it better and faster
We explore communication networks (signals, surface receptors, communication nodes...) that regulate the action of cancer cells and immune cells and seek to identify genetic alterations (from point mutations of a gene to complex chromosomal abnormalities) leading to the transformation of a healthy cell into a tumor cell.
This work has already helped improve our understanding of the disease, to better understand how immune cells fight it and the strategies used by tumor cells in an attempt to escape them. They also led to the discovery of new molecular targets that are now the subject of diagnostic and therapeutic applications in oncology.
As a consequence of its new organization, the CRCM has enriched both its research and its application areas to ensure better and faster understanding, diagnosis and treatment disease.
What are these new avenues of research and these new indications?
For the last four years we have focussed our energies on four priorities:
- Identification of molecules specifically expressed by tumor cells and validation of the therapeutic potential of these new targets.
- Understanding the complex mechanisms that govern the relationship between the tumor and its host and it manipulation to limit the formation of metastases.
- Updating of new biomarkers that can improve the classification of cancers and facilitate the diagnosis, prognosis and monitoring of the disease at all stages of treatment.
- Launching of innovative clinical trials within our fields of expertise and scientific treatment (breast, blood and digestive tract).
Finally, together with the Unit "Epidemiology and Social Sciences applied to medical innovation" of Jean-Paul Moatti, we assess the social, economic and cultural development of these new treatments: their cost, the growing complexity of treatment decisions under the combined effect of genetic tests and targeted therapies, the attitude of patients faced with the "chronicity" of their disease...
Understand and manipulate the mechanisms used by tumor cells to repair the damage done to its DNA and proliferate in a hostile environment.
At the same time, if we managed to transform some of our discoveries in diagnostic or therapeutic options, these discoveries have also opened new avenues of research.
The first of these, led by the CNRS and Robert Fuchs and Vincent Géli, is that of DNA repair. While continuing to identify and quantify the genetic alterations that lead to malignant transformation, we want to better understand the mechanisms involved in this damage and repair of damaged DNA. In addition to their pharmacological manipulation, the objective is to better contribute to the evaluation of this new class of drugs by our clinicians as we already do with HDAC and PARP inhibitors (the first corrects the defects of epigenetic regulation frequently encountered in cancer cells while the latter limits the ability of tumors to escape chemotherapy by preventing them from repairing the damage caused to their DNA).
In the case of pancreatic cancer, these genetic alterations are a conditional part of the malignancy. With the team of Juan Iovanna, the CRCM is now trying to answer another key question: when transformed, how do tumor cells manage to survive and thrive in the harsh environment that surrounds them (little or no oxygen, nutrients ...)? The goal this time is to identify a new therapeutic target able to lower the stress response of pancreatic cancer cells and thus make them more susceptible to the deleterious microenvironment. In this same direction, the team will seek to understand the stress response of prostate tumor cells.
What is the impact of these developments on the organization of the CRCM?
To encourage multidisciplinarity, accelerate innovation, but also to promote interfaces with scientists from other disciplines (immunology, chemistry, physics, computational biology ...), the CRCM will be organized into two distinct poles: the first will explore the molecular mechanisms that regulate oncogenesis and tumor dissemination, the second will be responsible for guiding the new targets from this research to applications in cancer and to evaluate the therapeutic potential of compounds derived from these new targets in animals and then in man.
What technologies are "hidden" in these innovations?
Thanks to engineering and technology accessible to the IPC or nearby, our scientists and clinicians develop their hypotheses and evaluate their potential in a wide variety of systems (from bacteria through the worm to humans) and scales: conventional genetics, sequencing, molecular profiling of tumors, proteomics, functional imaging, scientific imaging in vitro and in vivo, bioinformatics, biostatistics, studies of protein-protein interactions, cell therapy, design and production of monoclonal antibodies (including engineering of bifunctional antibodies).
Our work is also based on scientific and medical platforms that cover all stages of innovation: the sequential access to patient samples from our biobank, the preclinical evaluation of new compounds with TrGET®, early clinical trials of drug candidates with ETOH, evaluation of the immune response induced by these new treatments using the immunomonitoring platform and finally, with the support of the Department of Clinical Research and Innovation, the organization of clinical trials and the use of data from these studies.