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.
Those studies 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 of tumoral development.
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 unraveling the heterogeneity of CRC at the single-cell level as well as the plasticity of specific cellular states.
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Publications:
Wnt, Glucocorticoid and Cellular Prion Protein Cooperate to Drive a Mesenchymal Phenotype with Poor Prognosis in Colon Cancer. S. Mouillet-Richard, A. Gougelet, B. Passet, C. Brochard, D. Le Corre, C. L. Pitasi, C. Joubel, M. Sroussi, C. Gallois, J. Lavergne, J. Castille, M. Vilotte, N. Daniel-Carlier, C. Pilati, A. de Reyniès, F. Djouadi, S. Colnot, T. André, J. Taieb, J.-L. Vilotte, B. Romagnolo, P. Laurent-Puig. Journal of Translational Medicine, 2024, Vol. 22 pp. 337 Link.
PrPC Controls Epithelial-to-Mesenchymal Transition in EGFR-Mutated NSCLC: Implications for TKI Resistance and Patient Follow-Up. C. Lailler, A. Didelot, S. Garinet, H. Berthou, M. Sroussi, A. de Reyniès, S. Dedhar, S. Martin-Lannerée, E. Fabre, F. Le Pimpec-Barthes, A. Perrier, V. Poindessous, A. Mansuet-Lupo, F. Djouadi, J.-M. Launay, P. Laurent-Puig, H. Blons, S. Mouillet-Richard. Oncogene, 2024 Link.
Successive Next-Generation Sequencing Strategy for Optimal Fusion Gene Detection in Non-Small-Cell Lung Cancer in Clinical Practice. S. Garinet, A. Lupo, T. Denize, R. Loyaux, S. Timsit, B. Gazeau, E. Fabre, Z. Maaradji, L. Gibault, E. Giroux-Leprieur, B. Duchemann, I. Monnet, S. Jouveshomme, M. Aldea, B. Besse, F. L. Pimpec-Barthes, K. Leroy, M. Wislez, H. Blons. Pathology, 2024, Vol. 56 pp. 702–709 Link.
Clinical Value of Sequential Circulating Tumor DNA Analysis Using Next-Generation Sequencing and Epigenetic Modifications for Guiding Thermal Ablation for Colorectal Cancer Metastases: A Prospective Study. T. Boeken, O. Pellerin, C. Bourreau, J. Palle, C. Gallois, A. Zaanan, J. Taieb, W. Lahlou, A. Di Gaeta, M. Al Ahmar, X. Guerra, C. Dean, P. Laurent Puig, M. Sapoval, H. Pereira, H. Blons. La radiologia medica, 2024 Link.
A Novel Chr1-miR-200 Driven Whole Transcriptome Signature Shapes Tumor Immune Microenvironment and Predicts Relapse in Early-Stage Lung Adenocarcinoma. S. Garinet, A. Didelot, L. Marisa, G. Beinse, M. Sroussi, F. Le Pimpec-Barthes, E. Fabre, L. Gibault, P. Laurent-Puig, S. Mouillet-Richard, A. Legras, H. Blons. Journal of Translational Medicine, 2023, Vol. 21 pp. 324 Link.
Transcriptomic Signatures of MSI-High Metastatic Colorectal Cancer Predict Efficacy of Immune Checkpoint Inhibitors. C. Gallois, M. Landi, J. Taieb, M. Sroussi, B. Saberzadeh-Ardestani, A. Cazelles, S. Lonardi, F. Bergamo, R. Intini, G. Maddalena, F. Pietrantonio, F. Corti, M. Ambrosini, A. Martinetti, M. M. Germani, C. Boccaccio, G. Vetere, S. Mouillet-Richard, A. de Reynies, F. A. Sinicrope, C. Cremolini, P. Laurent-Puig. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 2023, Vol. 29 pp. 3771–3778 Link.
Maintenance Therapy With Cetuximab After FOLFIRI Plus Cetuximab for RAS Wild-Type Metastatic Colorectal Cancer: A Phase 2 Randomized Clinical Trial. V. Boige, H. Blons, E. François, M. Ben Abdelghani, J.-M. Phelip, V. Le Brun-Ly, L. Mineur, M. P. Galais, A.-L. Villing, V. Hautefeuille, L. Miglianico, C. De La Fouchardière, D. Genet, N. Levasseur, C.-B. Levaché, N. Penel, E. Mitry, S. Jacquot, T. Aparicio, E. Brument, S. Gourgou, F. Castan, O. Bouché. JAMA network open, 2023, Vol. 6 pp. e2333533 Link.
Circulating Tumour DNA at Baseline for Individualised Prognostication in Patients with Chemotherapy-Naïve Metastatic Colorectal Cancer. An AGEO Prospective Study. J.-B. Bachet, P. Laurent-Puig, A. Meurisse, O. Bouché, L. Mas, V. Taly, R. Cohen, J.-M. Gornet, P. Artru, S. Louafi, A. Thirot-Bidault, I. Baumgaertner, R. Coriat, D. Tougeron, T. Lecomte, F. Mary, T. Aparicio, L. Marthey, H. Blons, D. Vernerey, J. Taieb. European Journal of Cancer (Oxford, England: 1990), 2023, Vol. 189 pp. 112934 Link.
A Proof of Concept for Targeting the PrPC – Amyloid β Peptide Interaction in Basal Prostate Cancer and Mesenchymal Colon Cancer. S. Mouillet-Richard, S. Martin-Lannerée, D. Le Corre, T. Z. Hirsch, A. Ghazi, M. Sroussi, C. Pilati, A. de Reyniès, F. Djouadi, N. Vodovar, J.-M. Launay, P. Laurent-Puig. Oncogene, 2022, Vol. 41 pp. 4397–4404 Link.
Prognostic Relevance of Pancreatic Adenocarcinoma Whole-Tumor Transcriptomic Subtypes and Components. S. Zhao, R. Nicolle, J. Augustin, M. Svrcek, L. de Mestier, D. Le Corre, D. Pietrasz, O. Caliez, J. Cros, P. Laurent-Puig, J.-B. Bachet. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 2021, Vol. 27 pp. 6491–6499 Link.
Prognostic Value and Relation with Adjuvant Treatment Duration of ctDNA in Stage III Colon Cancer: A Post Hoc Analysis of the PRODIGE-GERCOR IDEA-France Trial. J. Taieb, V. Taly, J. Henriques, C. Bourreau, L. Mineur, J. Bennouna, J. Desrame, C. Louvet, C. Lepere, M. Mabro, J. Egreteau, O. Bouche, C. Mulot, K. Hormigos, K. Chaba, T. Mazard, A. de Gramont, D. Vernerey, T. André, P. Laurent-Puig. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 2021, Vol. 27 pp. 5638–5646 Link.
Intratumor CMS Heterogeneity Impacts Patient Prognosis in Localized Colon Cancer. L. Marisa, Y. Blum, J. Taieb, M. Ayadi, C. Pilati, K. Le Malicot, C. Lepage, R. Salazar, D. Aust, A. Duval, H. Blons, V. Taly, D. Gentien, A. Rapinat, J. Selves, S. Mouillet-Richard, V. Boige, J.-F. Emile, A. de Reyniès, P. Laurent-Puig. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 2021, Vol. 27 pp. 4768–4780 Link.