Tumor Dormancy Program

The therapeutic and scientific context

The campaign against cancer has made great progress over the last few decades, enabling more effective treatment of tumours. Unfortunately, the reoccurrence of cancer after therapy and a long period of remission (ranging from a few years to some decades) is still frequent in the form of local relapses or metastases. Thus, over 60% of the deaths linked to breast cancer occur later than 5 years after the first diagnosis and treatment. Likewise, the long-term survival rate for patients suffering from Acute Myeloblastic Leukaemia (AML) remains very low (just over 30%). Furthermore, the quality of life of the patients is greatly diminished by this very real possible threat of recurrence.

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Development of the observed quantity of leukaemia cells during a chemotherapy treatment and then during post-treatment monitoring

The short-term recurrence of a cancer may be explained by the phenomenon of resistance to treatments of the primary tumour. To the contrary, the recurrence or advent of metastasis in a patient after a full remission phase (lasting 5 to 25 years) can only be linked to the ability of certain tumour cells to persist after treatment whilst at the same time remaining inactive for a very long period. In this case, the patient may seem to have recovered but continues to carry a very small quantity of residual tumour cells in a state of dormancy.

This persistence of dormant residual cells occurs frequently and is difficult to detect. Succeeding in counteracting and combating this phenomenon will enable a remarkable advance for improving the survival of patients in the long term.

The mechanisms enabling the cells to enter or leave the state of dormancy are not well understood: the development of a balance between proliferation and apoptosis of the cells influenced by the tumour’s micro-environment, entry into quiescence, immune avoidance mechanisms, etc. The very nature of the residual cells is also the subject of debate: initial tumour cells or tumour cells which have mutated, small sub-populations of clones present right from the outset, tumour stem cells, etc. As these dormant cells are, by definition, in small quantities, they are difficult to detect and study and there are still few experimental models which would enable tumour dormancy to be studied.

The objective of the “Tumour Dormancy”program 2  is to take up this scientific challenge and develop a centre of scientific excellence in order to understand the mechanisms for tumour persistence and combat it. This program therefore includes a fundamental research section on putting together reliable experimental models for tumour dormancy, thereby enabling it to be studied, and a transverse research section aimed at improving means of detecting residual cells in patients and developing new drugs in order to target them.

The projects

The initial scientific projects sponsored by the program 2 are:

  • Study of the clonal heterogeneity of cases of acute myeloblastic leukaemia (C. Preudhomme, M. Cheok)
  • Targeting dormant tumour cells (B. Quesnel, C. Brinster, X. Thuru)
  • Study of the quiescence and activation of tumour stem cells (P. Formstecher, R. Polakowska, X. Le Bourhis, N. Prevaskaya, M. Corvaisier, R. Bourette)
  • The role of cell senescence in the phenomenon of tumour dormancy and the emergence of radiation-induced secondary sarcomas (C. Abbadie)
  • Study of the relevance of the canine model for prostate cancer and bone metastases in dogs (M. Duterque)
  • Identification of the molecular mechanisms causing the reprogramming of breast cancer stem cells (C. Lagadec)
  • Assessment of YAP/TEAD molecular interaction as a therapeutic target for control of the balance between dormancy and the activation of tumour cells (Prof. Patricia Melnyk, G. Huet, P. Cotelle)
  • Adaptation of dormant leukaemia cells to metabolic stress (P. Marchetti)
  • Improving diagnosis of residual leukaemia diseases by optimising the sequencing and bionformatics analysis of V(D)J rearrangements of the DNA of a lymphocyte population (M. Giraud)
  • Multi-patient analysis of genome markers (G. Marot)
  • The role of T lymphocyte response in the persistence of leukaemia (C. Brinster)
  • A physical and mathematical model for tumour proliferation and long-term cell degradation (from senescence to irradiation-induced damage) (F. Cleri)
  • An epigenomic approach to HOX-9 targeting in tumour dormancy (M-H. David-Cordonnier)

The actors

quesnel 380-480 copyrightThe “Tumor Dormancy”research program   is coordinated by the Professor Bruno Quesnel, a clinician and haematologist at the Lille CHRU and a researcher at INSERM. There, he directs the research team devoted to “Persistence factors for leukaemia cells” forming part of Mixed Research Unit UMR-S 1172 at the Jean-Pierre Aubert Research Centre located at the Lille Cancer Research Institute.

The program features 12 interdisciplinary research teams grouping together hospital practitioners (haematologists, dermatologists, etc.), biologists, veterinarians, chemists, mathematicians and computer scientists working at the CNRS, INSERM, the University of Lille, the Pasteur Institute in Lille, etc.