Documents pour «Cancer»

Expert panel discussions : why translational research matters

David Cameron

1h00min30

En point d'orgue du Scientific BRIO Day, David Cameron, spécialiste reconnu en Oncologie, Professeur  à l'Université d'Edimbourg, anime un débat sur la question de la recherche dite translationnelle, que l'on peut considérer comme le chaînon manquant entre recherche fondamentale et recherche clinique. Cette présentation a été donnée dans le cadre du Scientific BRIO Day 2 organisé annuellement par le SIRIC BRIO et qui a pour but de réunir tous les acteurs du SIRIC BRIO et plus largement de la cancérologie à Bordeaux.  

BRIO support to scientists

Damien DESSIS

13min29

BRIO management team was voluntarily built upon various competencies from different horizons (industry, charity…) to provide a broad skillset which aims at supporting the Bordeaux cancer research community. In this section, BRIO highlights the core support the team can bring to scientists. First, in an era of decreasing and competitive public funds, we look into other funding sources, such as European funds where BRIO and the University can assist in finding and applying to the right call for proposals. Considering the current trends of pharma R&D externalisation, a favorable environment exists to partner with the industry to develop new drugs or fund fundamental research related to marketed drugs or under development. BRIO can assist scientists with the industry interactions to build win-win partnerships. Finally, there are more than 300 scientists interested in cancer research in Bordeaux, all coming from various research disciplines but with limited interactions or knowledge of their peers. BRIO aims at providing solutions to facilitate interactions between scientists, develop new partnerships, improve translational research and build a strong and visible cancer research community.Cette présentation a été donnée dans le cadre du Scientific BRIO Day 2 organisé annuellement par le SIRIC BRIO et qui a pour but de réunir tous les acteurs du SIRIC BRIO et plus largement de la cancérologie à Bordeaux.

Multisarc

Antoine ITALIANO

13min09

Translational science : how to move from biology to clinical applications Soft-tissues sarcomas represent an heterogeneous group of tumors. Stadard of care is surgical resection followed by radiotherapy. Patients with metastatic relapse are treated with chemotherapy but the overall survival is only approximatly 18 months. Actual research try to define new therapeutic targets, adapted to the type of sarcoma. The personalized medicine project aims to propose to patients with advanced sarcoma a targeted therapy based on the genomic and immunilogical profile. The main difference with other projects resides in the genomic profile, which will be determined with a "whole genome" analysis.Cette présentation a été donnée dans le cadre du Scientific BRIO Day 2 organisé annuellement par le SIRIC BRIO et qui a pour but de réunir tous les acteurs du SIRIC BRIO et plus largement de la cancérologie à Bordeaux.

Translational cancer genomics and proteomics

Stefan SLEIJFER

29min17

Translational science : how to move from biology to clinical applicationsEvaluation of cell-free DNA (cfDNA) is a very attractive tool to serve as “liquid biopsy” to define and establish mutational changes in circulating tumor DNA (ctDNA) during cancer therapy.To identify tumor specific mutations in serum ctDNA associated with resistance against tamoxifen in metastatic breast cancer.Ten ER-positive metastatic breast cancer patients treated with first-line tamoxifen with blood sera available at start therapy (S1), during treatment (S2) and at disease progression (S3) were selected. DNA from normal and primary tumor tissue and cfDNA from sera were sequenced using the Ion Torrent Personal Genome Machine (Ion-PGM). In total 1,242 exons of 45 genes were sequenced up to 5,000 reads depth coverage and single nucleotide variants (SNVs) with at least 2% frequency were defined. Identified SNVs were re-sequenced for confirmation or checked by snapshot assays.The initial analyses revealed 246 SNVs in at least one serum sample, including 96 variants observed at disease progression in serum S3. The 96 variants contained 11 SNVs that were also present within the primary tumor in 6 patients. Re-sequencing at deeper level confirmed all 11 tumor SNVs. These variants occurred in 9 genes and were predicted pathogenic for CDH1, CREBBP, NF1, PIK3CA, SMAD4, and TP53. The variants for CDH1, CREBBP, and SMAD4 were not previously considered tumor-specific in publically available repositories. The remaining 85 variants at disease progression were only observed in serum, and covered 45 serum SNVs merely detected in serum S3 of above 6 patients. Of the 45 SNVs, 3 were already reported in cancer for BRCA1, MAP3K1 and PTCH1, with the first two SNVs considered pathogenic. Moreover, only one not yet reported SNV for AKAP9 (H562Q) was detected in all three sera but not in the tumor within one patient. Re-sequencing of these 4 serum SNVs confirmed only the AKAP9 variant, which is not known yet to be involved in tumor biology.Twelve variants occurring in 10 genes were identified and confirmed after re-sequencing in primary tumor DNA and serum taken at progression, which may be associated with tamoxifen therapy resistance and/or reflecting tumor load. Four of these SNVs have not been linked to to cancer before. Further studies are needed to explore the clinical relevance of the variants as tumor marker or a marker explaining tamoxifen resistance.Cette présentation a été donnée dans le cadre du Scientific BRIO Day 2 organisé annuellement par le SIRIC BRIO et qui a pour but de réunir tous les acteurs du SIRIC BRIO et plus largement de la cancérologie à Bordeaux.

Nutrition and cancer

Isabelle BOURDEL-MARCHASSON

25min07

Non-pharmaceutical medical innovations and public healthCancer and nutrition are closely related. According to epidemiological studies, western life style is a risk factors for the most frequent cancers and public health intervention aimed to reduce cancer incidence with public education. When cancer is present, malnutrition is frequent mainly due to cancer cachexia. In non-surgical patients prognosis is in great part predicted by MNA (mini-nutritional assessment), a tool closed to PG-SGA used to assess malnutrition adult patients with cancer. However, a large study did not show any effect of nutritional support on one-year mortality in older patients undergoing chemotherapy for solid tumours. Some other ways to control deleterious effect of cancer cachexia are explored with ongoing clinical trials: physical activity, anti-myostatin substances, immuno-modulating factors and short term fasting during chemotherapy.Cette présentation a été donnée dans le cadre du Scientific BRIO Day 2 organisé annuellement par le SIRIC BRIO et qui a pour but de réunir tous les acteurs du SIRIC BRIO et plus largement de la cancérologie à Bordeaux.

Curing leukemia ?

François-Xavier MAHON

19min53

Non-pharmaceutical medical innovations and public healthThe use of tyrosine kinase inhibitors (TKIs) targeted against the BCR-ABL1 oncoprotein has proven remarkably successful in chronic myeloid leukemia (CML) and long-term survival has become a reality. Despite this outstanding progress, detection of minimal residual disease precludes therapy termination in most TKI-receiving patients. CML has thus turned into a chronic illness, raising concerns about long-term safety, medication adherence and healthcare costs. Although treatment cessation may be feasible in few selected patients achieving deep molecular responses, a definitive cure remains elusive owing to the discovery that TKIs spare quiescent leukemic stem cells (LSC). Understanding mechanisms underlying LSC behavior in TKI-treated patients may provide important clues to develop an array of strategies that ensure the complete destruction of LSC reservoirs and thereby offer CML patients a definitive cure.Cette présentation a été donnée dans le cadre du Scientific BRIO Day 2 organisé annuellement par le SIRIC BRIO et qui a pour but de réunir tous les acteurs du SIRIC BRIO et plus largement de la cancérologie à Bordeaux.

Standardizing G8 evaluation

Pierre-Louis SOUBEYRAN

15min01

Non-pharmaceutical innovations and public healthManagement of the frail elderly with cancer is a challenge. Beside a poor outcome as compared to younger subjects, physicians will face increased risk of treatment-induced toxicity but also unexpected adverse events because of the underlying comorbidities and potential major consequences of these toxicities on the outcome because of frailty. In depth evaluation of the patient through geriatric assessment has been demonstrated as predictive of these adverse events but is time-consuming so that only a minority of cancer treatment hospitals will be able to propose it. Screening is part of the solution and G8 one of the best questionnaires currently available. Yet we have to go beyond this step and precisely define what to do for the unfit patients that we are now able to identify.Cette présentation a été donnée dans le cadre du Scientific BRIO Day 2 organisé annuellement par le SIRIC BRIO et qui a pour but de réunir tous les acteurs du SIRIC BRIO et plus largement de la cancérologie à Bordeaux.  

Innovation reimbursement

Christian FILLATREAU

09min11

Interface technology/clinical/SHS/public health : case study interventional radiology Novel diagnostic and therapeutic strategies is a continuum of 3 strongly associated phases : clinical research, medico-economic evaluation of a novel strategy and deployment of innovation, the last one being a field of competence of centers of expertise such as SIRIC BRIO.In the full cycle of innovation, the money time is the major challenge of a large deployment. The main problem is to find money. But, in 2015, 3 changes should improve the innovation continuum. Should it be a progress, an obstacle, or both ?...Cette présentation a été donnée dans le cadre du Scientific BRIO Day 2 organisé annuellement par le SIRIC BRIO et qui a pour but de réunir tous les acteurs du SIRIC BRIO et plus largement de la cancérologie à Bordeaux.

Cost-effectiveness analysis for decision making, illustrated theory

Antoine Bénard

19min21

Interface technology/clinical/SHS/public health : case study interventional radiologyIn a health care system with limited resources, each euro invested in a health care intervention is no longer available for another intervention. This imposes the need for a prioritization of health care interventions according to their additional value for money for maximizing health at a given cost. Cost-effectiveness analyses may answer two main questions: 1) does an intervention present sufficient value for money to be funded within a health system? The decision is based on the absolute value of the incremental cost-effectiveness ratio; 2) is further research needed to inform the decision (reduce uncertainty)? This involves bayesian value of information analyses.Cette présentation a été donnée dans le cadre du Scientific BRIO Day 2 organisé annuellement par le SIRIC BRIO et qui a pour but de réunir tous les acteurs du SIRIC BRIO et plus largement de la cancérologie à Bordeaux.

Sociology contribution to understanding the (no)diffusion of a medical innovation

Philippe GORRY

18min29

Interface technology/clinical/SHS/public health : case study interventional radiology We will present results of an undergoing study on the socioeconomic processes of recognition in oncology of a long-standing medical innovation, the so-called interventional radiology (IR). This project is conducted by a multidisciplinary team gathering health sociologist, sociologist of science, economist of innovation, health lawyer and interventional radiologist, supported by INCa. With scientometrics and patent landscaping, we get an understanding of the IR discoveries’ chronology and identify the relationships established between science, medicine and industry. Through field observations and semi-directed interviews, we analyzed the strategies of legitimation of IR, seeking to show how each social groups (physicians, hospital, public agency, industry, …) participate together or not in IR recognition and therefore built the normative framework for this innovative medical practice.Cette présentation a été donnée dans le cadre du Scientific BRIO Day 2 organisé annuellement par le SIRIC BRIO et qui a pour but de réunir tous les acteurs du SIRIC BRIO et plus largement de la cancérologie à Bordeaux.

Technique, research and benefits

Jean PALUSSIERE

22min11

Interface technology/clinical/SHS/public health : case study interventional radiology  >> Jean PalussièreRadiology in oncology or so called interventional oncology is now considered by certain as the fourth oncological discipline, alongside surgical, radiation, and medical oncology. This makes it particularly dynamic and it is important for interventional radiologists to stay on top of technological developments. During the last ten years the therapeutic part of Interventional Oncology has rapidly grown in different fields such as thermal ablation and local drug delivery. Thermal ablation, which allows to treat tumors with temperature modifications, has known an increasing development during the last 10 years to treat metastases and primary tumors. In particular, they offer an alternative to patients contraindicated or refusing surgery. The main advantages are the low invasiveness with a high level of tolerance, and a low rate of complications and also the repeatability in patients whose disease may be chronic. Since 2004 we have applied these thermal ablation techniques to breast cancer with interesting results for patients in the elderly. We are now preparing the development of a non invasive ablative technique based on focused ultrasounds guided by MRI. MRI guided Focused Ultrasound is one of the primary areas of research of the Translational Research and Advanced Imaging Laboratory (TRAIL) University of Bordeaux.For the last 10 years, a team of researchers at the University of Utah, under the direction of Dennis L. Parker, have been developing MRI guided FUS technology. In collaboration with Image Guided Therapy of Pessac, and with funding from the National Institutes of Health, they have developed a breast-specific MRI guided FUS system and are now at a point where the system could be applied to subjects at the University of Bordeaux. Through this partnership, we hope to develop this pioneering endeavour and to improve the treatment of breast cancer.>> Nicolas GrenierRadiology (IR) is a growing field, mainly in oncology. It is minimally invasive, preserving body integrity, with less side-effects and has also a real economic impact due to : short recovery, ambulatory patient care and maintaining the patient in his social environment with less days off.IR has also an advantage being based on many technical innovations and investments by companies is high in this field. It allows combination of strategies such as identification of specific targets using molecular imaging (another growing field), development of focal therapies and combination with new medical targeted therapies and nanotechnologies for local drug delivery or local onset of biological effects (gene expression…).Unfortunately, IR is also slowered in its deployment essentially due to problems of funding innovation by our regulation authorities, but also due to some lack in organization of evaluation of clinical and economic impacts of such innovations by the involved scientific societies.As an example, this presentation will show how, by using a combination of strategies of innovations, we have been tried, for the last 7 years, to develop a specific targeting of prostatic cancer in order to offer new focal therapies.Cette présentation a été donnée dans le cadre du Scientific BRIO Day 2 organisé annuellement par le SIRIC BRIO et qui a pour but de réunir tous les acteurs du SIRIC BRIO et plus largement de la cancérologie à Bordeaux.  

BRIO's facts and figures, structuration projects : Axe Cancer, translational research centerUpdate the implementation of BRIO

Pierre-Louis SOUBEYRAN

13min02

Update the implementation of BRIO Brio organisation is now fully up and running, and more than 100 research projects are currently active into the 6 integrated research programmes. In addition, major progresses were achieved at the level of the 7 strategic axes defined to structure and support cancer research in Bordeaux. The bioinformatics axis saw the recruitment of 4 bioinformaticians (2 funded by BRIO) and the creation of a transversal bioinformatics axis at the University. For the in-vivo research axis, a project to develop a translational research center is currently being developed (see Bordeaux Cancer section). A new Inserm candidate unit “Cancer Epidemiology and Environmental Exposures” is being proposed to consolidate the health outcome axis. Databases have been the topic of the first inter-SIRIC collaboration and 4 working groups have been defined. The personalised medicine axis is being supported by BRIO-funded technicians and will be further consolidated with a post-doctoral fellow. A new HHS group was formed to support HHS projects in cancer and a call for proposals will be launched in 2015. Finally, the fundamental axis saw the creation of a transversal cancer axis at the University, complementary to BRIO activities and focusing on technologies and fundamental research. In parallel, BRIO also started its communication activities and 14 events were organised or supported in 2014 to facilitate interactions between scientists, develop new partnerships and create a cancer research community in Bordeaux. Cette présentation a été donnée dans le cadre du Scientific BRIO Day 2 organisé annuellement par le SIRIC BRIO et qui a pour but de réunir tous les acteurs du SIRIC BRIO et plus largement de la cancérologie à Bordeaux.