P. Cordelier

  Molecular heterogeneity of pancreatic tumors

 

Our research project at a glance

Pancreatic tumors display a remarkable molecular variability that results in a unique ability to escape and survive therapy. Our research effort is dedicated to improve the molecular understanding of pancreatic tumors and therefore to better address the role of intra-tumor heterogeneity in diagnosis and the development of therapeutic resistance.

Objectives

Our general objective is to better understand the complex relationship between molecular heterogeneity and therapeutic resistance of pancreatic adenocarcinoma (PDAC), to help alleviate the dismal prognosis of this disease with no cure.

To this end, we developed basic research programs to investigate the function of candidate proteins involved in the fine-tuning of mitosis, DNA damage repair and replication, and tumor metabolism. We found that these proteins are heterogeneously expressed in patients and control experimental tumors growth. In cohorts of patients, we identified specific molecular signatures, including circulating, noninvasive nucleic acids for patients’ stratification.

In parallel we created with LAAS-CNRS novel nanodevices for candidate biomarker identification / quantification.

Last, we are engaged in bench-to-bedside, personalized, translational preclinical programs and first-in-man clinical trials using gene therapy to defeat pancreatic tumor resistance to conventional chemotherapy and next-generation immunotherapies.

We expect that our scientific program will bring new insights in the molecular heterogeneity of tumors, to develop innovative strategies that will overcome pancreatic adenocarcinoma resistance to treatment.

Key words

 

  • Pancreatic cancer
  • Molecular heterogeneity
  • DNA damage repair
  • Mitosis
  • DNA replication
  • Tumor metabolism
  • Gene therapy
  • Oncolytic virus

 

Labels and networks

Selected publications


2017

Buscail, L

Pancreatic cancer: Exosomes for targeting KRAS in the treatment of pancreatic cancer Journal Article

Nat Rev Gastroenterol Hepatol, 14 (11), pp. 636-638, 2017, ISSN: 1759-5053 (Electronic) 1759-5045 (Linking).

Links | BibTeX

2016

Chaveroux, C; Bruhat, A; Carraro, V; Jousse, C; Averous, J; Maurin, A C; Parry, L; Mesclon, F; Muranishi, Y; Cordelier, P; Meulle, A; Baril, P; Do Thi, A; Ravassard, P; Mallet, J; Fafournoux, P

Regulating the expression of therapeutic transgenes by controlled intake of dietary essential amino acids Journal Article

Nat Biotechnol, 34 (7), pp. 746-51, 2016, ISSN: 1546-1696 (Electronic) 1087-0156 (Linking).

Links | BibTeX

2015

Buscail, L; Bournet, B; Vernejoul, F; Cambois, G; Lulka, H; Hanoun, N; Dufresne, M; Meulle, A; Vignolle-Vidoni, A; Ligat, L; Saint-Laurent, N; Pont, F; Dejean, S; Gayral, M; Martins, F; Torrisani, J; Barbey, O; Gross, F; Guimbaud, R; Otal, P; Lopez, F; Tiraby, G; Cordelier, P

First-in-man phase 1 clinical trial of gene therapy for advanced pancreatic cancer: safety, biodistribution, and preliminary clinical findings Journal Article

Mol Ther, 23 (4), pp. 779-89, 2015, ISSN: 1525-0024 (Electronic) 1525-0016 (Linking).

Links | BibTeX

Ligat, L; Saint-Laurent, N; El-Mrani, A; Gigoux, V; Al Saati, T; Tomasini, R; Nigri, J; Dejean, S; Pont, F; Baer, R; Guillermet-Guibert, J; Cordelier, P; Lopez, F; Dufresne, M

Pancreatic preneoplastic lesions plasma signatures and biomarkers based on proteome profiling of mouse models Journal Article

Br J Cancer, 113 (11), pp. 1590-8, 2015, ISSN: 1532-1827 (Electronic) 0007-0920 (Linking).

Links | BibTeX

2014

Hanoun, N; Fritsch, S; Gayet, O; Gigoux, V; Cordelier, P; Dusetti, N; Torrisani, J; Dufresne, M

The E3 ubiquitin ligase thyroid hormone receptor-interacting protein 12 targets pancreas transcription factor 1a for proteasomal degradation Journal Article

J Biol Chem, 289 (51), pp. 35593-604, 2014, ISSN: 1083-351X (Electronic) 0021-9258 (Linking).

Links | BibTeX

2013

Al Saati, T; Clerc, P; Hanoun, N; Peuget, S; Lulka, H; Gigoux, V; Capilla, F; Beluchon, B; Couvelard, A; Selves, J; Buscail, L; Carrier, A; Dusetti, N; Dufresne, M

Oxidative stress induced by inactivation of TP53INP1 cooperates with KrasG12D to initiate and promote pancreatic carcinogenesis in the murine pancreas Journal Article

Am J Pathol, 182 (6), pp. 1996-2004, 2013, ISSN: 1525-2191 (Electronic) 0002-9440 (Linking).

Links | BibTeX

Sicard, F; Gayral, M; Lulka, H; Buscail, L; Cordelier, P

Targeting miR-21 for the therapy of pancreatic cancer Journal Article

Mol Ther, 21 (5), pp. 986-94, 2013, ISSN: 1525-0024 (Electronic) 1525-0016 (Linking).

Links | BibTeX

2010

Hanoun, N; Delpu, Y; Suriawinata, A A; Bournet, B; Bureau, C; Selves, J; Tsongalis, G J; Dufresne, M; Buscail, L; Cordelier, P; Torrisani, J

The silencing of microRNA 148a production by DNA hypermethylation is an early event in pancreatic carcinogenesis Journal Article

Clin Chem, 56 (7), pp. 1107-18, 2010, ISSN: 1530-8561 (Electronic) 0009-9147 (Linking).

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2009

Bournet, B; Souque, A; Senesse, P; Assenat, E; Barthet, M; Lesavre, N; Aubert, A; O'Toole, D; Hammel, P; Levy, P; Ruszniewski, P; Bouisson, M; Escourrou, J; Cordelier, P; Buscail, L

Endoscopic ultrasound-guided fine-needle aspiration biopsy coupled with KRAS mutation assay to distinguish pancreatic cancer from pseudotumoral chronic pancreatitis Journal Article

Endoscopy, 41 (6), pp. 552-7, 2009, ISSN: 1438-8812 (Electronic) 0013-726X (Linking).

Links | BibTeX

2007

Torrisani, J; Unterberger, A; Tendulkar, S R; Shikimi, K; Szyf, M

AUF1 cell cycle variations define genomic DNA methylation by regulation of DNMT1 mRNA stability Journal Article

Mol Cell Biol, 27 (1), pp. 395-410, 2007, ISSN: 0270-7306 (Print) 0270-7306 (Linking).

Links | BibTeX