Tumor Resistance Program

Context and objectives

The last fifteen years of fundamental and clinical research have enabled huge advances in the effectiveness of anti-cancer treatments in the fields of surgery, chemotherapy and radiotherapy.

In spite of these advances, certain forms of cancer and certain patients show innate or acquired resistance to treatments which then leads on to failures in therapies which are prejudicial to the patients’ recoveries.

The objective of the “Tumor Resistance” program, is to be able to better predict, prevent and combat this phenomenon involving tumour and host resistance to locoregional treatments by closely associating clinical and fundamental research.

It will be possible to achieve these objectives if we are capable of identifying the resistance phenomenon (ideally prior to treatment) and selecting the most effective therapies.

This involves achieving a better understanding of the cell mechanisms involved in resistance: identification of the cell receptors and messengers, deciphering the intracellular signalling routes, and the influence of the tumour micro-environment. This will enable new therapeutic targets to be defined and consequently the development of more effective treatments.

As the phenomenon of the resistance of tumour cells is not limited to the tumours in a particular organ, the research projects for this program relate to the various types of cancer: gastro-oesophageal cancer, upper airway tract cancer, lung cancer, pancreatic cancer, cancer of the liver, the kidneys, the ovaries, etc.

The research themes

Five themes have been developed as part of program 1:

  1. Understanding the cell mechanisms involved in the resistance phenomenon and identifying new biomarkers enabling this resistance to be observed and predicted. All of these fundamental and translational research projects call on in vitro approaches (cell models), in vivo models (animal models for spontaneous tumours (dogs, cats) or preclinical transgenic models for induced tumours (mice, zebrafish) and ex vivo (patients’ tissues).
    • Study of the MET route in lung cancer resistance (D. Tulasne)
    • The impact of the HGF-SF-MET signalling pathway, heparanase and hypoxia on acquired tumour resistance (J. Vicogne)
    • The impact of the TrK signalling pathway and of NGS in resistance to targeted therapies for breast cancer (R. Toillon)
    • The role and targeting of the MUC4-ErbB2 complex in the resistance of pancreatic adenocarcinoma to chemotherapy treatments (N. Jonckheere)
    • Gastric adenocarcinoma featuring independent cells: Identification of resistance biomarkers and of new target molecules (M. Messager)
    • Angiogenesis, tumour endothelium and immunological avoidance of tumours (F. Soncin)
  2. Developing new imaging tools for improving early diagnosis, detecting and foreseeing resistance to treatments, and better monitoring the patient after treatment.
    • Molecular identification of brain tumours (gliomas) and detecting their resistance to therapies using mass spectrometry (I. Fournier)
    • Targeted photodynamic therapy of lesions found in ovarian peritoneal carcinomatosis (P. Collinet)
    • The impact of Positron Emission Tomograph scanning on assessment of the effectiveness of radiochemotherapy (G. Piessen)
  3. Identifying and proposing new targets for therapies.
    Under this programme’s framework, the following are studied:

    • Targeting the MET cell receptors involved in lung cancer resistance (D. Tulasne)
    • Targeting the EGF1/2 domains of MUC4 mucin for the development of new inhibitors that act as anti-cancer agents (I. Van Seuningen)
    • Targeting calcium stress in order to improve the effectiveness of chemotherapies (F. Vanden Abeele)
    • Study of an innovative immunotherapy strategy targeting regulatory T lymphocyte cells (N. Delhem)
  4. Improving clinical and therapeutic approaches in order to avoid or reduce the development of the resistance of the tumour or patient.
    Under this programme’s framework, the following are being developed:

    • A national FREGAT (French Research in EsoGastric Tumours) Clinical and Biological Database dedicated to study of resistance to treatments for gastro-oesophageal cancer (INCa quality label, C. Mariette) https://www.fregat-database.org linked to the FREGAT national clinical research network.
    • A study of the heterogeneousness of the expression of the MET cell receptor involved in the development of lung cancer tumour cells (A. Cortot)
    • Development of a Monte Carlo calculation algorithm for a dose measurement based on radiotherapy MRIs (N. Reynaert)
  5. Lastly, in close collaboration with the transverse program for Human and Social Sciences, understanding and combating the phenomenon of reluctance and difficulties in accessing healthcare which lead to delays in the diagnosis, treatment and care of patients. Human and Social Sciences Program

The actors

cristophe-mariette-113x150The “Tumor Resistance” program is coordinated by the Professor Christophe Mariette, who is a Professor of Surgery and a Doctor of Science. He practices at the Huriez Hospital of the Lille CHRU as the Head of the Department of General and Digestive Surgery. Prof. Mariette has a strong involvement in clinical research into digestive oncology in his surgical practice and in terms of fundamental and translational research as the co-ordinator of ONCOLille’s “Tumor Resistance” Program 1 .

van-seuningen-360-480-113x150Doctor Isabelle Van Seuningen is a co-coordinator of the program 1. Dr. Van Seuningen is a 1st Class Research Director at the CNRS and is responsible for the INSERM team “Mucins, differentiation and epithelial carcinogenesis” with INSERM Mixed Research Unit UMR-S 1172 at the Jean-Pierre Aubert Research Centre. The research themes developed within her team are: 1) Understanding the role MUC1 and MUC4 mucins play in epithelial carcinogenesis, and; 2) Understanding resistance mechanisms in gastro-oesophageal cancer, pancreatic cancer, colon cancer and renal cancer.

Keywords for program 1:

Resistance, gastro-oesophageal cancer, adenocarcinoma involving independent cells, lung cancer, pancreatic cancer, therapy targeting, targeted therapy, biomarkers, diagnosis, prognosis, predictive marker, immunotherapy, angiogenesis, tumour micro-environment, tumour heterogeneousness, cell signalling, imaging, animal models, physical models.