Research project

Genetics of solid tumors

Florence PEDEUTOUR, Professor-Clinician, PU-PH1

Our clinical activity and our research programs have been devoted to improvement of diagnosis and care management of bone and soft tissue tumors. Our research is currently focused on the genomic and functional characterization of adipose tissue tumors.Adipose tissue tumors constitute a large group of tumors including frequent benign forms (lipomas) and malignant forms, liposarcomas.

- Liposarcomas: the most frequent sarcomas are still in need of efficient treatments

The most common type of liposarcomas is represented by the atypical lipomatous tumors/ well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS). Whereas WDLPS are locally aggressive but virtually never metastasize, DDLPS have metastatic potential and their prognosis is poor: the five-year mortality rate is 30%. Efficacy of conventional chemotherapy treatments is limited in DDLPS. The very few targeted therapies available so far have been disappointing.

The identification of novel therapeutic targets in WDLPS/DDLPS is therefore our objective.

- Looking for novel therapeutic options: the FGF/FGFR pathway, a novel target in the treatment of WDLPS/DDLPS ?

We have chosen to concentrate our research efforts on the determination of the role of the FGF/FGFR signalling pathway in WDLPS/DDLPS aiming at rapid therapeutic applications following our results on human cellular models.

We are using human WDLPS and DDLPS cell lines that have been established by our team and are therefore fully characterized and validated as well as a large collection of primary tumors.

Our project associates 4 teams with a longstanding collaboration: 3 teams from Nice (Nice University Hospital/IRCAN, Nice University Hospital, Comprehensive Cancer Center Centre Antoine Lacassagne) and one team from Bordeaux (Comprehensive Cancer Center Institut Bergonié). These 4 teams provide expertise in the clinics, pathology and molecular genetics of sarcomas as well as in biostatistics.

We are investigating:

- the expression and localisation of FGFRs and FGFs in WDLPS/DDLPS and the prognostic value of FGFR expression by correlation of the expression data with the patient clinical outcomes

- the mechanisms of sensitivity and resistance to FGFR inhibitors of the liposarcoma cells 

- the effect of FGFR inhibitors alone or in combination with other antagonists on liposarcoma tumorigenesis both in vitro and in vivo using xenograft models.

Our objective is to transfer our results from the bench to the patient bed. Thus, our ultimate goal is to improve patient management by taking advantage of the position of our collaborator Prof. A. Italiano as head of the early phase trial unit in Institut Bergonié.

Research teams