EA 3836 – ONCOPHARMACOLOGY LABORATORY OF ANTOINE LACASSAGNE CENTER

The Oncopharmacologie laboratory, created in 1987, has been attached to the University of Nice Sophia-Antipolis since 2002 as a university hospitality team (EA 3836) “Pharmacological targeting unit in oncology” which combines a PU-PH in medical oncology and two PU-PH in head and neck surgery.
The goal of this EA is to optimize medication management through a personalized medical approach that allows cancer treatment to be oriented according to individual characteristics specific to the patient’s tumor (search for tumor mutations, etc.), or in relation to the patient (genetic characteristics intrinsic to the patient). The goal is to adapt the treatment to each patient in order to administer the right treatment at the right dose. In this context, the laboratory carries out both a hospital activity, and a translational research activity: pre-clinical activity (on small animals) and clinical activity.
This unit has recently evolved into a dual unit integrating the topics of medical oncology and advanced radiotherapy. The new title will be “Unit of Pharmacogenetics and Radiogenetics of Cancers” (UPRC) headed by Gerard Milano.

LINES OF RESEARCH

The research activity, dedicated to translational research, is divided into two areas: pre-clinical research and clinical research.
The main objective of pre-clinical work which is carried out on models of human tumor xenografted lines in immunodeficient mice, is to test combinations of new drugs (targeted treatments, immunotherapy, or conventional cytotoxic agents), associated or not with radiotherapy, for the purpose of providing rational bases for the design of original clinical trials, in particular in ENT pathology.
Clinically oriented work is mainly done through multicenter prospective studies designed to identify predictors of resistance or sensitivity and / or toxicity to anticancer treatments. These approaches include either intrinsic patient characteristics (pharmacogenetic studies of constitutional polymorphisms from a simple blood sample), or tumor-specific characteristics (somatic mutations, etc.). There is also a research activity in the field of pharmacokinetics, mainly in the context of Phases I-II, with the objective of highlighting relationships between pharmacokinetic parameters and toxicity and / or the efficacy of the treatment enabling an optimal therapeutic window to be defined for a given treatment, in order to achieve individual dosage adjustments. These clinical research programs are mainly conducted in colorectal cancers, ENT cancers and breast cancers, in cooperation with national groups such as GERCOR or GORTEC. This research is funded by the Ministry of Health or through trials promoted by the pharmaceutical industry.

The unit has strong local partnerships with teams from IRCAN (G. Pages) and iBV (E. van Obberghen).
At the regional level, within the framework of the PACA Cancéropôle, the unit has collaborated for a long time with the pharmacokinetics department of the Marseille Faculty of Pharmacy.
At the national level, the team is coordinating multi-center clinical translational research studies (including a PHRC, among others, on securing fluoropyrimidine treatments, including meta-analyzes in partnership with Gustave Roussy, and surveys of clinical practice in partnership with the FFCD).
At the international level, the group refers to its original work on dihydropyrimidine dehydrogenase (DPD), and collaborates in this context with Professor A. Van Kuilenburg (Amsterdam, The Netherlands). Close collaboration has also been established with Professor M. Merlano’s team (Cuneo, Italy) for pre-clinical studies in particular.

The Oncopharmacology laboratory is involved in the following courses

  • various national IUDs in oncology.
  • National Chemistry Course of the IGR.
  • Reception of trainees from different sectors of scientific training in the Nice region.
  • reception of Master II students
  • reception of students (doctors for the most part) in university thesis.

The laboratory has significantly contributed to the training and obtaining of critical publications of future PU-PH physicians at local and national level.

GENETIC

NGS MiniSeq (ILLUMINA) NGS MiniSeq (ILLUMINA)

 

droplet

Droplet PCR (Bio-Rad QX200)

 

 

maasarray

MassARRAY Analyzer 4 (Sequenom Agena) with chip 96 spots

 

 

 

lightcycler

LightCycler 480 (PCR quantitative), Roche, with block 96

 

 

 

sequenceur

Sequencer – Beckman CEQ 8800

 

 

 

 

PHARMACOCINETIC

 

upcl

UPLC-MSMS (Xevo TQD Waters)

Publications

The Oncopharmacology team at Lacassagne has published more than 300 articles in international peer-reviewed journals and regularly presents papers at major American conferences in the specialty (ASCO, AACR).

Five main publications of the last 5 years

– Van Kuilenburg AB, Etienne-Grimaldi MC, Mahamat A, Meijer J, Laurent-Puig P, Olschwang S, Gaub MP, Hennekam RC, Benchimol D, Houry S, Letoublon C, FN Gilly, Pezet D, Andre T, Faucheron JL , Abderrahim-Ferkoune A, Vijzelaar R, Pradere B, Milano G. Frequent intragenic rearrangements of DPYD in colorectal tumors. Pharmacogenomics J. 2015; 15 (3): 211-8.

-Thariat J, Bensadoun RJ, Etienne-Grimaldi MC, Grall D, Penault-Llorca F, Dassonville O, Bertucci F, Cayre A, De Raucourt D, Geoffrey L, Finetti P, Giraud P, Racadot S, Morinière S, Sudaka A , Van Obberghen-Schilling E, Milano G. Contrasted outcomes to tumor geometry in IGF1R expression in head and neck cancer patients receiving postoperative chemoradiation (GORTEC trial 2004-02). Clin Cancer Res. 2012; 18 (18): 5123-33.

-Thariat J, Etienne-Grimaldi MC, Grall D, Bensadoun RJ, Cayre A, Penault-Llorca F, Veracini L, Francoual M, Formento JL, Dassonville O, De Raucourt D, Geoffrey L, Giraud P, Racadot S, Moriniere S , Milano G, Van Obberghen-Schilling E. Epidermal Growth Factor Receptor protein detection in head and neck cancer patients: a many faceted picture. Clin Cancer Res. 2012; 18 (5): 1313-1322.

-Bozec A, Sudaka A, Etienne-Grimaldi TM, Brunstein Mc, Fischel JL, Milano G. Antitumor activity of cetuximab associated with taxotere-cisplatin-fluorouracil (TPF) combination on an orthotopic head and neck cancer model. Oral Oncol. 2011; 47 (10): 940-5.

 

equipe
Medical staff
Gérard Milano, Ph D
Marie-Christine Etienne-Grimaldi, Pharmacien biologiste, Responsable Qualité du Pôle des Laboratoires

Evelyne Zanghellini, health executive
Nathalie Ebran, engineer
Patricia Formento, Senior Technician
Laurence Llorca, technician
Hedi Ben Yahia, technician
Fabienne Lopez, medical assistant