What signals do cancer cells send to prevent these therapies from working?
A targeted therapy is a therapy that prevents a specifically active signal in tumour cells. Our team is interested in inhibitors of PI3Ks, innovative targeted therapies for solid and liquid cancers. PI3Ks are proteins that are hyperactive in cancer and are present in several forms, called isoforms. In this study, which has just been published in Molecular Cancer Therapeutics, journal of the American Association Against Cancer (AACR), we investigated the response of tumour cells to therapies targeting PI3Ks isoforms using comprehensive proteomics approaches. We validated a novel combination therapy in patient cell cultures that inhibits this tumour cell response and consequently increases the efficacy of PI3K inhibitors in treating pancreatic cancer.
This work involved multiple collaborations in Toulouse, with the IPBS proteomics team, the IUCT-O biological resource centre, as well as with the laboratories of Dr Reichert in Munich, Dr Hirsch and Dr Cappello in Turin, and led to the defence of a thesis funded by the Ligue Nationale Contre le Cancer.
Discover the published article :
Mol Cancer Ther. 2021 Sep 22;molcanther.0981.2020. doi: 10.1158/1535-7163.MCT-20-0981. Online ahead of print.
Phosphoproteomics identifies PI3K inhibitor-selective adaptive responses in pancreatic cancer cell therapy and resistance
Celia Cintas, Thibault Douche, Zahra Dantes, Emmanuelle Mouton-Barbosa, Marie-Pierre Bousquet, Coralie Cayron, Nicole Therville, Frédéric Pont, Fernanda Ramos-Delgado, Camille Guyon, Barbara H Garmy-Susini, Paola Cappello, Odile Burlet-Schiltz, Emilio Hirsch, Anne Gomez-Brouchet, Benoît Thibault, Maximilian Reichert, Julie Guillermet-Guibert
Key Words :
- Pancreatic cancer,
- targeted therapies,
- cell signalling networks,
- translational research,
- therapeutic combinations
Collaborations, acknowledgements and associated patents
This work was mainly funded by :
- Ligue Nationale contre le cancer
Fondation pour la Recherche Médicale
1: Guillermet-Guibert J*, Douche T, Mouton-Barbosa E, Schiltz O, Bousquet M, Cintas C WO2019101871-A1 New phosphopeptide useful for predicting sensitivity of cancer cells to p110-alpha and/or p110-gamma inhibitor, or treating cancer e.g. pancreatic cancer in mammals.
2: Guillermet-Guibert J*, Reichert M, Cintas C. WO2019073031-A1 Treatment of pancreatic cancer, particularly pancreatic ductal adenocarcinoma, by administering combination of p110alpha selective inhibitor and p110gamma selective inhibitor. Forcheur Jean-Marie Lehn International prize
CRCT Team : SigDYN : Integrated cell signalling and class I-II-III isoforms of PI3K