Focus on the 9 key Cancer and Cognition periods – Flashback
Beforre 2007: few tools, many complaints
The impacts of cancer as well as its treatments (chemotherapy, targeted therapy) on cognitive functions are poorly known. The question deserved weak interest among the scientific community. Nevertheless, several studies dealing with this problem were published mainly on breast cancer patients. However, because of very low number of patients in studies and due to the lack of longitudinal clinical investigations, in addition to the absence of dedicated animal models, there were no truly satisfactory studies to assess the mechanisms relating cancer to cognition.
Therefore, the issue deserves major attention: for many years, the oncologists are attentive to patient complaints of persistent memory, concentration and thinking déficits.
2007: the Cancéropôle Nord-Ouest (CNO) as a pioneer
Since 2007, the Cancéropôle Nord-Ouest (CNO) develops a research axis entitled ” Cancer and Neurosciences “. In the same time, under the impulsion given by Pr Florence Joly (medical oncologist in the Center François Baclesse of Caen), a key program “Cancer and Cognition” completely dedicated to the study of the impact of the cancer and its treatments on patient’s cognitive functions , rapidly sets up. It mobilizes different sites of the CNO (Caen, Rouen, Lille, Brussels) and consists of oncologists concerned by the clinical research, researchers specialized in human and social sciences, and also in psychology, and of research teams with expertise in Neurosciences to conduct cancer patient brain imaging and to study the involved cellular and molecular mechanisms.
This program, multidisciplinary and original, has no equivalent Within the French countryside, and the CNO aims to be positioned as a national leader in the research on the cognition of cancer patients treated by chemotherapy and/or targeted therapy.
The first project – called COG-AGE – is ambitious, transversal and innovative: studying specifically the impact of the adjuvant chemotherapy in elderly patients treated for a localized breast cancer by developing concomitantly animal models. This project was supported by the CNO, INCA and by the Sanofi-Aventis pharmaceutical Laboratory.
2008: international recognition
Thanks to the CNO, a first national organized seminar “cancer and cognitive function” took place in Normandy (Deauville) which played a major role in the consolidation of the pioneer group. The clinical and research teams from Rouen, Caen, Lille and Brussels had positioned as cancer and cognition pioneers in France. The ICCTF – International Cognition and Cancer Task Force – then acknowledged the CNO working group and suggested they take part in specific workshops as well as in the writing of draft guides on neuropsychological evaluation in oncology.
The implementation into national and international networks thus began, enabling the validation of a tool – the FACT-Cog, developed with CORES (Center of Outcomes, Research and Education de Chicago). Since this work, there was a questionnaire to evaluate cognitive impairment perceived by patients. Other pilot projects were launched. Our Cancer and Cognition program had finally succeeded in attracting the scientific community’s interest on Cancer and Cognition
2011: Original research on targeted therapies
The consortium “Cancer et Cognition” initiates original studies both with patients and animal models in order to investigate the impact of targeted therapy on cognitive functions:
- A national longitudinal experimental clinical trial COG-ANGIO, conducted by Cancéropôle Nord-Ouest (CNO), demonstrated for the first time that anti-angiogenic targeted therapy hase a direct negative impact on the cognitive functions of patients treated for a metastatic kidney cancer.
- Angiogenesis inhibitors were also assessed in a preclinical behavioural model with BEVACIZUMAB and a specific antibody directed against the murine VEGF (Material Transfer Agreement between Genentech US – ROCHE France and the Cancer and Cognition platform members).
2012: an international conference of first importance
The consortium ” Cancer et Cognition ” from the Cancéropôle Nord-Ouest now benefits from an international visibility through the integration into the International Cancer and Cognition Task Force (ICCTF) in which it represents the French country.. Thus, the consortium is in charge of the organization of the international meeting of the ICCTF in Paris from 15 till 17 March 2012. This major event which gathers more than 200 participants coming from different countries, consolidates its leading role in the field.
2013: positive reports at all levels
The solid support of the Cancéropôle Nord-Ouest both in terms of human resources and fundings of programs dealing with “Cancer and Cognition ” allowed great advances, and thus the legitimacy and the acknowledgment of the consortium continuously grow.. The study results, and in particular the COG-AGE trial, are presented as two oral communications in the American Society of Clinical Oncology (ASCO).
The consortium initiatesthe 2nd national interCancéropôles/INCA workshop (June, 2013) in Lille under the theme “cognitive functions and cancer “. Also, it participates to the 1st Interregional day “Cancers and Neurosciences” co-organized by the GIRCI and the Cancéropôle Grand Est. The consortium integrates the European Task Force “Cancer and Cognition ” of the EORTC.
2014: the animal model is paying off
- The study developed in young and old mice allowed to highlight aged-related specific mechanisms as well as modification of the behavioural flexibility and alteration of neurogenesis in the dentate gyrus of the hippocampus after the 5 Fluorouracile (5-FU) chemotherapy, mechanisms compensated by a co-administration of glucose (Dubois et al., 2014a, Neuropharmacology «Chemotherapy-induced long-term alteration of executive functions and hippocampal cell proliferation: role of glucose as adjuvant “).The molecule Everolimus (inhibitor of the mTOR pathway), did not induce alteration of cognitive functions (unprecedented study financed by NOVARTIS). The signal for the oncologists is strong and very important: from now, they can prescribe this molecule to their patients, by ensuring the relative safety of this molecule on cognitive capacities (Dubois M and al ., on 2014 Plos One ” Evaluation of the impact of the cancer therapy everolimus on the central nervous system in mice “)
2015: Lauching of the Cancer and Cognition platform
Improving the care of the aftereffects of the cancer and treatments is now acknowledged as an objective of the 2015-2019 Cancer Plan of the French government’s (action 8-3). The question of the impact of the cancer and its treatments seems then integrated into current therapeutic developments
This unique multidisciplinary expertise in France developed by the Cancéropôle Nord-Ouest can be used by the scientific and medical community and the pharmaceutical industries through our innovative platform “Cancer and Cognition “. Big Pharma can now find expertise in evaluating the impact of cancer therapy on quality of life and cognition, in both pre-clinical models and preclinical trials
2016: French League Against Cancer label
The Cancer and Cognition platform obtained the French League Against Cancer label in 2016.
Opening to other partnerships
Collaborations were introduced and implemented with :
- UMR 6301 CNRS-CEA-UCBN « Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales » (ISTCT), Caen
- L’UMR 8257 Cognac G, Paris
- PSY-NCA, Rouen
- L’Ecole Normale Supérieure, Cachan
- OncoNeurotox, Paris
- Hopital du Val de Grâce, Paris
- Hopital Pitié-Salpétrière, Paris
These partnerships provide to the CNO team additional expertise on central nervous system tumours. This expertise will entail synergistic work between neuropsychologists, statisticians, computer experts, ergonomics experts, oncologists and neurologists, and will aim to ensure national visibility.
The objective is to expand the competencies and partnerships of the CNO platform on a national level.