Personalized Medicine and Pharmacogenomics Group

Over the past years, we have contributed to several studies that have profiled the molecular landscape of several types of solid tumours including colorectal cancer (CRC) and pancreatic cancer. The definition of molecular classifications has allowed to shed light on the diversity of CRC or pancreatic tumours. Concerning lung cancer, we are studying tumour heterogeneity through the prism of clinical outcome. These transcriptomic studies are based on bulk data, which is the result of a dialogue between tumor cells, stromal cells and immune cells. They have opened new questions that we are now investigating:
· what are the molecular mechanisms orchestrating the emergence and/or maintenance of different subtypes of a given cancer?
· what is the degree of heterogeneity between different areas of the tumor or between primary and the different metastatic sites?
· how does this signature evolve under treatment?
· how can we substitute this tissue signature by surrogate circulating markers facilitating the transfer to the clinics?
· and finally, by deciphering the different pathways driving each subtype, how can we improve CRC treatment?
We are tackling these issues by leveraging several patient cohorts to which we have access through our close link with various hospitals (HEGP, La Pitié-Salpétrière, and others) or our involvement in different cooperative cancer groups at national and international level (EORTC, FFCD, GERCOR, IFCT) and also by our deep implication in the SIRIC CARPEM (www.carpem.fr). As a complementary approach, we are developing cell-based assays to gain insight into molecular and biological processes. In addition to these large-scale, unbiased studies, we are developing projects focused on specific potential drivers or antagonists of aggressive subgroups of cancer such as microRNAs of the miR-200 family in lung cancer associated with epithelial-to mesenchymal-transition or the cellular prion protein PrPC in the mesenchymal subgroup of colorectal cancer.
Our key current project that actually integrates all the above-mentioned issues aims at unravelling the heterogeneity of CRC at the single-cell level as well as the plasticity of specific cellular states.

Publications:

Bachet J-B, Blons H, Hammel P, Hariry IE, Portales F, Mineur L, Metges J-P, Mulot C, Bourreau C, Cain J, Cros J, Laurent-Puig P. Circulating Tumor DNA is Prognostic and Potentially Predictive of Eryaspase Efficacy in Second-line in Patients with Advanced Pancreatic Adenocarcinoma. Clin Cancer Res. 2020;26(19):5208‑16.

Le Corre D, Ghazi A, Balogoun R, Pilati C, Aparicio T, Martin-Lannerée S, Marisa L, Djouadi F, Poindessous V, Crozet C, Emile J-F, Mulot C, Le Malicot K, Boige V, Blons H, de Reynies A, Taieb J, Ghiringhelli F, Bennouna J, Launay J-M, Laurent-Puig P, Mouillet-Richard S. The cellular prion protein controls the mesenchymal-like molecular subtype and predicts disease outcome in colorectal cancer. EBioMedicine. 2019;46:94‑104.

Laurent-Puig P, Grisoni M-L, Heinemann V, Liebaert F, Neureiter D, Jung A, Montestruc F, Gaston-Mathe Y, Thiébaut R, Stintzing S. Validation of miR-31-3p Expression to Predict Cetuximab Efficacy When Used as First-Line Treatment in RAS Wild-Type Metastatic Colorectal Cancer. Clin Cancer Res. 2019;25(1):134‑41.

Gallois C, Taieb J, Le Corre D, Le Malicot K, Tabernero J, Mulot C, Seitz J-F, Aparicio T, Folprecht G, Lepage C, Mini E, Van Laethem J-L, Emile J-F, Laurent-Puig P, PETACC8 investigators. Prognostic Value of Methylator Phenotype in Stage III Colon Cancer Treated with Oxaliplatin-based Adjuvant Chemotherapy. Clin Cancer Res. 2018;24(19):4745‑53.

Legras A, Barritault M, Tallet A, Fabre E, Guyard A, Rance B, Digan W, Pecuchet N, Giroux-Leprieur E, Julie C, Jouveshomme S, Duchatelle V, Giraudet V, Gibault L, Cazier A, Pastre J, Le Pimpec-Barthes F, Laurent-Puig P, Blons H. Validity of Targeted Next-Generation Sequencing in Routine Care for Identifying Clinically Relevant Molecular Profiles in Non-Small-Cell Lung Cancer: Results of a 2-Year Experience on 1343 Samples. J Mol Diagn JMD. 2018;20(4):550‑64.

Bachet JB, Bouché O, Taieb J, Dubreuil O, Garcia ML, Meurisse A, Normand C, Gornet JM, Artru P, Louafi S, Bonnetain F, Thirot-Bidault A, Baumgaertner I, Coriat R, Tougeron D, Lecomte T, Mary F, Aparicio T, Marthey L, Taly V, Blons H, Vernerey D, Laurent-Puig P. RAS mutation analysis in circulating tumor DNA from patients with metastatic colorectal cancer: the AGEO RASANC prospective multicenter study. Ann Oncol. 2018;29(5):1211‑9.