The cell signalling enzymes PI3Kalpha and PI3Kβ play major roles in the body.

PI3Ks are important molecules that, by adding a kind of tag to a lipid, induce messages (also called signals) in cells. They are therefore key regulators of cell signalling. In higher order animals, such as humans, PI3Ks come in different flavours. In particular, PI3Kalpha and PI3Kbeta work together to orchestrate key cellular and organ processes, such as cell migration, proliferation, or the formation of vascular and lymphatic vessels, regulation of blood sugar and other metabolic processes, control of organ organisation, growth and turnover, fertility, immune responses and blood clotting. Consequently, their dysregulation leads to several diseases, such as cancer, diabetes, inflammatory diseases and hypergrowth syndromes. Here we review the progress made by our scientific community over the past 15 years in understanding and targeting these proteins. Inhibitors of PI3Ks are already being used to treat breast cancer patients; new applications based on the knowledge gained are in the pipeline.

This work on isoforms has led to the filing of several patents.

• Treating micrometastatic disease comprises administering phosphoinositide 3-kinase alpha selective inhibitor Patent Number: WO2021001431-A1 ; Patent Assignee: INSERM NAT SANTE & RECH MEDICALE INST; UNIV TOULOUSE III SABATIER PAUL ; Inventor(s): GUILLERMET-GUIBERT J; THIBAULT B; RAMOS DELGADO C F; et al.
• 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 mammal, preferably human, comprises amino acid sequence Patent Number: WO2019101871-A1 EP3713963-A1 US2020355693-A1 Patent Assignee: INSERM INST NAT SANTE & RECH MEDICALE; UNIV TOULOUSE III SABATIER PAUL; CNRS CENT NAT RECH SCI Inventor(s): GUILLERMET-GUIBERT J; DOUCHE T; MOUTON-BARBOSA E; et al.
• Treatment of pancreatic cancer, particularly pancreatic ductal adenocarcinoma, by administering combination of p110alpha selective inhibitor and p110gamma selective inhibitor Patent Number: WO2019073031-A1 EP3694511-A1 Patent Assignee: INSERM NAT SANTE & RECH MEDICALE INST; UNIV TOULOUSE III SABATIER PAUL; CNRS CENT NAT RECH SCI; et. Al Inventor(s): GUILLERMET-GUIBERT J; REICHERT M; CINTAS C.

Discover the published article :

Biochem J. 2021 Mar 26;478(6):1199-1225.doi: 10.1042/BCJ20210004.
Organismal roles for the PI3Kα and β isoforms: their specificity, redundancy or cooperation is context-dependent
Silvia Arcucci, Fernanda Ramos-Delgado, Coralie Cayron, Nicole Therville, Marie-Pierre Gratacap, Céline Basset, Benoit Thibault, Julie Guillermet-Guibert

Key words :

• Cellular signalling,
• Cancer,
• Oncogenic signalling,
• tumour suppressors,
• PI3K/AKT/mTOR

Collaborations and acknowledgements

Julie Guillermet-Guibert’s laboratory has been labelled by ARC (PJA20171206596), the ANR Toucan Laboratory of Excellence, MSCA-ITN/ETN PhD-PI3K (Project ID: 675392, Thesis funding of Silvia Arcucci and Fernanda Ramos-Delgado), Fondation de France (funding of Benoit Thibault), GSO, Fondation Toulouse Cancer Santé, Regeneve (Région Midi-Pyrénées/FEDER), ANR-JCJC RADIANCE (funding of Benoit Thibault), Ligue Nationale Régionale contre le Cancer (funding of Coralie Cayron), Fonroga Prize ( Coralie Cayron) and Inca Plan Cancer. “

Contact:

Dr Julie Guillermet-Guibert
CRCT team: SigDYN: Integration of cellular signals & PI3K class I, II, III.
Mail : julie.guillermet@inserm.fr

One picture

Roles of PI3K and PI3Kβ in organism