Predictive Oncology

Paoli Calmettes Institute

Predictive Oncology

Paoli Calmettes Institute

Our team brings together multidisciplinary profiles working together to develop tools that will ensure better management of aggressive solid tumors.

Our scientific priority is to combat aggressive or treatment-resistant metastatic breast and colon cancers. To this end, we are developing so-called "precision medicine" strategies (Figure 1).

Figure 1. General workflow. Figure generated with Canva.

To guide our projects, the team is headed by François Bertucci and Emilie Mamessier, two recognized experts in their respective fields.

  • François Bertucci is a medical oncologist and pioneer in tumor profiling. He is also head of the Translational Research Committee at the Institut Paoli Calmettes.
  • Emilie Mamessier is a researcher at INSERM, specializing in transfer research.

This co-direction enables us to combine innovative technical and scientific developments on relevant clinical issues, all thanks to valuable patient samples.

A multidisciplinary team

Our projects benefit from the involvement of a team of around twenty members, experts in a wide range of disciplines: bioinformatics, immunology, molecular and cellular biology, etc.

State-of-the-art equipment

In addition to the equipment available at CRCM, our laboratory has its own resources for carrying out our research (see figure 2):

  • Devices and robots for next-generation sequencing (NextSeq500, Robot Magnis)
  • Transcriptomics (Affymetrix) and On-chip comparative genomic hybridization (Agilent) platforms
  • Equipment for isolating DNA (BioRad droplet generator and reader) and circulating tumor cells (Parsortix, micromanipulator)
  • Microfluidic devices (Ibidi, Fluigent, peristaltic pump)
  • Real-time imaging system and microscopy
  • Cell culture rooms dedicated to human samples

 

Our mission

Together, we are working to :

  • Refine tumor classification,
  • Offer more therapeutic options,
  • Optimize treatment strategy,
  • A better understanding of resistance mechanisms,
  • A better understanding of metastatic processes.

This relies on the design of prospective clinical trials to collect samples at different stages of the disease and associated clinical data. This approach is essential, particularly for newer treatments for which only limited data are available.

Figure 2. All the techniques/technologies used in the team are designed to adapt to patient samples and meet clinical needs: tumor profiling and classification, single-cell resolution computational approaches, multiplexed immunofluorescence on FFPE tissue, patient tumor-derived organoids (single or complex co-culture), analysis of liquid biopsies, identification of new targets and design of new treatments. Figure generated with BioRender.

Key words

  • Treatment resistance
  • Aggressive cancers
  • Drug-conjugated antibodies
  • Circulating tumor cells
  • Tumor microenvironment

To tackle the issue of treatment resistance, we have structured our research program around 5 axes.

The projects

Tumor cell plasticity and the dynamics of treatment response
There are very few consensus biomarkers of response/resistance reported for each treatment. One of the reasons for this is the lack of resolutive analysis of timely samples (pre-, per- and post-treatment, and at progression) to identify the multiple mechanisms selected by treatment.

We aim to fill this gap using recent technologies (RNAseq from small, degraded, formalin-fixed samples) and/or preclinical models ( patient-derivedtumor organoids, patient-derived xenografts...) that we are developing in the laboratory.

These topics are covered in the Tumor Profiling and Preclinical Models groups. For further information, please contact F Bertucci, E Mamessier
The role of intratumoral heterogeneity in response to treatment
The tumor cells making up a tumor are heterogeneous, and this heterogeneity can be the cause of early relapse.

We aim to assess this heterogeneity in different types of cancer and at different stages of the disease(characterization at tissue and single-cell level), provide tools to measure the degree of heterogeneity in each tumor (multiplexed immunofluorescence of tumor cells and their microenvironment), and propose new markers and therapeutic combinations to overcome this heterogeneity (computational analysis, in vitro / in vivo tests).

This topic is covered in the Tumor heterogeneity in space and time group. For further information, please contact F Bertucci, E Mamessier and E Denicolaï.
Providing new treatments for aggressive tumors
When a tumor becomes resistant to a treatment, one strategy is to attack the resistance mechanism with the aim of achieving a lasting response.

We are developing pre-clinical models that enable us to test new therapeutic combination, without increasing overall toxicity.

This topic is addressed in the New therapeutic strategies and Preclinical models groups. For further information, please contact F Bertucci, E Mamessier and O Cabaud.
Early detection of treatment resistance with liquid biopsies
The earlier resistance to a treatment is detected, the sooner the clinician can take action and propose an ad-hoc therapeutic strategy.

We are therefore looking for new markers of resistance to treatment using liquid biopsies, which are minimally invasive methods that give us access to tumor material from a simple blood test.

This topic is covered in the Circulating Tumor Cells group. For further information, please contact E Mamessier and E Denicolaï.
Mechanisms of tumor cell survival during the metastatic cascade
When tumor cells metastasize, they are exposed to stress factors and mechanical forces that can kill them. However, some cells develop strategies to circumvent these stresses and continue their journey until they reach a new niche. This topic is addressed in the laboratory by E. Mamessier (identification and targeting of survival mechanisms in response to stress using patient-derived samples such as FFPE tissue, CTCs and PDTOs) and by C. Aquaviva (microfluidic approaches).

For further information, please contact E Mamessier and C Acquaviva.

In a nutshell

June 2023 – The OncoPredic team
Blue Mars 2024
The November 2024 team

Team news

featured publications

05/2024

Bertucci F, de Nonneville A, Finetti P, Cohendet A, Guille A, Mamessier E

04/2017

M-Rabet M, Cabaud O, Josselin E, Finetti P, Castellano R, Farina A, Agavnian-Couquiaud E, Saviane G, Collette Y, Viens P, Gonçalves A, Ginestier C, Charafe-Jauffret E, Birnbaum D, Olive D, Bertucci F, Lopez M.

11/2017

Birnbaum DJ, Finetti P, Birnbaum D, Mamessier E, Bertucci F.

Labels, Funding and Partners

Alumni

Like others, they were part of the team.
Thank you to all those who have contributed to CRCM's excellence and impact.

Daniel Birnbaum
DR0 Emeritus Researcher, CRCM, INSERM, CNRS, AMU Director of the Predictive Oncology Team
then Emeritus Researcher
Séverine Garnier
Research engineer
INFINITy, Inserm U1291, Toulouse
Anaïs Aulas
Project leader and visiting scientist
AmyPore, France Neuroscience Center, HiLIFE, Helsinki Finland
Post-doctoral fellow
Ludovic Berger
Doctorant / PhD student
Maria Lucia Liberatoscioli
Medical biologist
Doctorant / PhD student
Alexia Lopresti
Post-doc Erler Group, BRIC,
University of Copenhagen, Denmark
Doctorant / PhD student
Marwa Manai
Assistant professor Institut Pasteur, Tunis, Tunisia
Doctorant / PhD student

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