Intercellular COMMUnication in CANcer biology and Therapy
The cancer treatments are either nonspecific (radiotherapy, chemotherapy) and destroy all the cellular components of the tumor whether they are protective or not, or “too” specific (targeting a particular cellular component in the tumor) which leads has resistance to treatment and relapse. Understanding the heterogeneity of tumors in order to characterize the communications between tumor cells, healthy stromal cells, vessels, immune cells and extracellular matrix is necessary to propose a treatment with a suitable specificity. The objective of this program is to propose new treatments to increase the survival rate of patients by acting on the entire microenvironment and to exceed the limits of traditional treatments. To do this, COMMUCAN (Intercellular Communication in Cancer Biology and Therapy) studies the contribution of this communication to the failures of some of the current treatments and develops new therapeutic strategies based on 3D images of the tumor and not only on the targeting of metabolic pathways .
COMMUCAN should allow:
- Identify new communication networks within the tumor microenvironment involved in tumor progression and metastasis;
- Continue clinical and preclinical research for newly identified targets and biomarkers;
- Develop new therapies based on a more comprehensive understanding of tumor biology and communications between different cell types;
- Development of therapeutic and diagnostic nanotechnologies targeting elements of the tumor microenvironment;
- Develop mathematical models and computational methods of disease modeling as well as predictive models of clinical outcomes focusing on tumor and tumor microenvironment interactions;
- Apply the principles and conceptual analysis of evolutionary economics to better understand tumor progression.
Andreas Bikfalvi, Julie Déchanet-Merville and Alain Ravaud co-coordinate all the research of the COMMUCAN project within BRIO, in constant link with the manager program. They set up the main strategic axes of the clinical and preclinical research of the program, in accordance with the budgets, the competitive and medical environment. They co-lead the 2 annual program progress meetings as well as the preparation meetings of the Scientific Advisatory Board (SAB) (1 to 2 meetings / year).
BRIO referee: Andreas Bikfalvi (Professor in Cellular and Molecular Biology, Director Inserm U1029, University of Bordeaux)
Expertise: Tumor Invasion, Angiogenesis
Andreas Bikfalvi’s group has expertise in all areas of cancer biology and in vitro and in vivo studies. The goal of the unit is the understanding of tumor interactions with the microenvironment and the identification of targets for therapeutic purposes. Current research topics in this team are:
– The identification of molecular networks in renal cell carcinomas with clear cells and gliomas
– The signaling mechanisms involved in the invasion of tumor cells
– The involvement of CXC chemokines in the development of the tumor
Reference BRIO: Majid Khatib (Biologist, Director Inserm U1029, University of Bordeaux)
Majid Khatib‘s group is interested in the reprogramming of tumor activity and its microenvironment using different models in vitro and in vivo (mouse, zebrafish). Current research projects are:
– Role of protein processing in the malignant and metastatic phenotype
– Therapeutic targets in colorectal cancer and renal cell carcinoma
– Protein Maturation and Immune Responses
BRIO referee: Frédéric Saltel (Biologist, Team Leader BaRITOn, Inserm U1053, Platform ONCOPROT, University of Bordeaux), Violaine Moreau (Biologist, Team Leader BaRITOn, Inserm U1053, University of Bordeaux)
Expertise: Tumor Invasion, Angiogenesis
The research object of the BaRITOn team is the understanding of the molecular basis of tumor cell invasion. She develops in vitro and in vivo studies to address the involvement of targeted proteins in this process as well as holistic approaches to identify key markers and actors involved in tumor cell invasion. This team has extensive expertise in actin-based processes such as cell migration and invasion and are experts in the field of invadomas. V. Moreau has a strong expertise in Rho GTPase signaling. F. Saltel developed the Oncoprot platform dedicated to proteomic analysis of tissue sections. This analysis is a new method for identifying new biomarkers.
BRIO referee: Julie Déchanet-Merville (CNRS Research Director, Director of UMR 5164, ImmunoConcept, University of Bordeaux), Benjamin Faustin (Immunologist, CNRS UMR5164, ImmunoConcEpT, University of Bordeaux), Nicolas Larmonier (Immunologist, CNRS UMR5164, ImmunoConcEpT, University of Bordeaux), Thomas Pradeu (Philosopher, CNRS UMR5164, ImmunoConcEpT, University of Bordeaux)
Expertise: Immunology, Philosophy
This team is dedicated to the physiological and pathological role of the immune system through basic and translational research. She has extensive experience in immunomonitoring normal or pathological specimens and has developed in vitro and in vivo models of cancer. She has expertise in mAb generation as well as phenotyping using high throughput multiparametric flow cytometry. They have long-standing expertise in cohort analysis of patients through relationships with several clinical departments and blood bank of Bordeaux University Hospital. Their laboratory includes all the technologies necessary for the development of their research program (flow cytometry, viral vectorology, histology, qPCR). Thomas Pradeu’s group deals with the philosophy of biology, medicine and conceptual-theoretical biology.
BRIO referee: Rodrigue Rossignol (Research Director, Cellomet CEO, Inserm U1211, University of Bordeaux)
This team has recognized international expertise in the study of energy metabolism in physiology and pathology. Rodrigue Rossignol is also CEO of Cellomet, a CRO technology platform dedicated to the study of metabolic remodeling triggered by tumor development, drug resistance and anticancer drug activity. At the preclinical stage, the team is developing precision bioenergetic medicine strategies for lung cancer that combine the inhibition of molecular oncology targets with the bioenergetic stratification of tumors. CELLOMET provides pharmaceutical companies with services to decipher the metabolic impact and toxicity of various anti-cancer compounds.
BRIO referee: Franck Couillaud (Research Director IMOTION)
Expertise: Imaging and multifunctional contrast agents
The imaging team aims to develop novel therapeutic strategies for the treatment of solid tumors and the tumor microenvironment and to develop innovative therapies. The research program includes image-guided thermotherapies and the validation of therapeutic agents for diagnosis and therapy. IMOTION is intrinsically a translational research team that includes experimental researchers and clinicians. IMOTION manages VIVOPTIC, a preclinical imaging platform from the University of Bordeaux (CNRS UMS 3427 / Inserm US 3757).
Référents BRIO : Sébastien Lecommandoux (Directeur LCPO, CNRS Chercheur), Olivier Sandre (Directeur de recherche CNRS), Elisabeth Garanger (CNRS chercheur)
BRIO referrals: Sébastien Lecommandoux (LCPO Director, CNRS Researcher), Olivier Sandre (CNRS Research Director), Elisabeth Garanger (CNRS researcher)
Expertise: Chemistry – Synthesis of nanoparticles and functionalization
The team “self-assembly Polymers & Life Sciences” belongs to the LCPO, a joint research unit of the University of Bordeaux dedicated to the science of polymer materials.
The areas of expertise of this group are:
– The design and assembly of polypeptide and polysaccharide block copolymers for intelligent drug delivery,
– The design of complex self-assembled nanostructures mimicking viruses or cells,
– The development of know-how in the formulation of polymer and hybrid nanoparticles
The team has extensive experience in translational projects dedicated to cancer therapy and imaging at the national and international levels.
BRIO referee: Pierre Nassoy (CNRS Research Director)
Expertise: Microfluidic techniques and cellular encapsulation
The biophysical team has developed a cell encapsulation technique using microfluidic technology. This technology has been applied to several cell types, including tumor cells, and will be used in COMMUCAN projects for encapsulation of tumor and stromal cells.
BRIO referee: Masha Nikolski (CNRS Research Director)
Expertise: Functional genomics and biostatistics of clinical and experimental data
The CBiB team is made up of scientists and engineers whose fields of interest range from biological data analysis to computer science. CBiB provides bioinformatics solutions to biotech, pharmaceutical, clinical and research communities. The work involves the development of statistical models, algorithms, and computational methods to analyze large sets of “omics” data.
BRIO referee: Rodolphe Thiebaut (Deputy Director Inserm U1219, director of the SISTM team)
Expertise: Functional genomics and biostatistics of clinical and experimental data
The SISTM team is dedicated to the development of statistical methods for integrative data analysis in medicine and biology. The challenge is to analyze BIG DATA data to answer clinical and biological questions using appropriate statistical methods. The methods are mainly based on mechanistic modeling using differential equation systems or statistical learning methods. This team is one of the few teams to benefit from the recognition of the two national institutes Inserm and Inria.
Reference BRIO: Olivier Saut (Research Director of the ONCology Modeling Project “MONC”, CNRS UMR 5251 Mathematical Institute of Bordeaux), Thierry Colin (Mathematician, INRIA)
Expertise: Computer Modeling
The INRIA Monc project team develops new tools for clinical decision support using mathematical modeling and artificial intelligence approaches. The scientific fields mobilized are numerous: mechanistic modeling, scientific computing, data assimilation, image processing, statistical learning and neural networks. It aims to answer the important questions that biologists or doctors ask themselves about the knowledge of the disease, its treatments or its follow-up. The issues addressed are, for example, the study of the interactions of different mechanisms influencing the progression of the disease, the detection or diagnosis of lesions using imaging, or the early evaluation of the efficacy of a treatment.
BRIO referee: Philipe Gorry (Medical geneticist)
The social sciences team is a joint research laboratory between the University of Bordeaux and the CNRS. One of the research programs focuses on the economics of science, innovation and industrialization, through empirical and theoretical approaches, including scientometry, patent mapping, network analysis , econometrics and agent-based modeling.
Expertise: Bordeaux University Hospital is involved in standard care with a critical number of patients. This provides access to quality medical records and pathological tumor samples of colon cancer (Prof. E. Rullier, Prof. C. Laurent, Prof. JF Blanc, Dr. D Smith), renal cell carcinoma (Pr. A Ravaud, Prof. JC Bernhard) and glioblastoma (Prof. H Loiseau). Certified national data collections are implemented in the national clinical and biological database with pathological information integration and additional information on molecular biology (Dr M.Yacoub).
Expertise: The Digestive Tumor Unit of the Institut Bergonié has a long experience in clinical research on colorectal cancer and more specifically on their metastases. The team was among the first to prospectively validate the concept of parenchymal protection approaches using intraoperative radiofrequency ablation. Particularly involved in clinical research methodology, the EORTC SURCARE platform was created to develop prospective (mainly phase 4) studies in collaboration with the European Society of Surgical Oncology. Two prospective studies are underway on colorectal liver metastases (CLIMB EORTC 1409, DREAM EORTC 1527) based on a European clinical network (more than 15 reference centers), extended in Japan with collaboration with JCOG and more recently with MD Anderson. The EORTC will set up a centralized biobank based on these studies and will feed several international translational research programs. In summary, the team is leading a large international clinical network in surgical oncology that offers significant prospective resources for translational studies.
Clinical Research & Translational Studies
+ Metabolic Stress in the Immune Function of T Cells, Macrophages and Dendritic Cells
Cells, june 2018
Domblides C, et al.
+ Systemic chemotherapy plus cetuximab after complete surgery in the treatment of isolated colorectal peritoneal carcinoma: COCHISE phase II clinical trial.
BMC research notes, Juil 2019
Evrard S, et al.
+ Deciphering the complex role of thrombospondin-1 in glioblastoma development.. Nature Comm in press.
Nature communication, Mar 2019
Daubon T (co-corresponding author), Léon C, et al.
+ The Multiple Layers of the Tumor Environment.
Trends in cancer, Dec 2018
Laplane L, et al.
+ DDR1 and DDR2 physical interaction leads to signaling interconnection but with possible distinct functions.
Cell adhesion and migration, 2018
Croissant C, et al.
+ Methods for Mapping the Extracellular and Membrane Proteome in the Avian Embryo, and Identification of Putative Vascular Targets or Endothelial Genes.
Methods in molecular biology, 2018
Kilarski WW, et al.
+ Inactivation of Proprotein Convertases in T Cells Inhibits PD-1 Expression and Creates a Favorable Immune Microenvironment in Colorectal Cancer
Cancer research, oct 2019
Tomé M, et al.
+ Combining laser capture microdissection and protemics reveals an active translation machinery controlling invadosome formation.
Nature communication, May 2018
Ezzoukhry Z, et al.
+ Preparation and Properties of Asymmetric Synthetic Membranes Based on Lipid and Polymer Self-Assembly.
Langmuir, Mar 2018
Peyret A, Zhao H, Lecommandoux S.
+ Inactivation of proprotein convertases in T cells inhibits PD-1 expression and creates a favorable immune microenvironment in colorectal cancer.
Cancer Research, Jul 2019
Tomé M, et al.
+Nuclear control of lung cancer cells migration, invasion and bioenergetics by eukaryotic translation initiation factor 3F
Oncogene, Sept 2019
Esteve P, et al.