PI3Ks are important molecules, that, by adding a tag on a lipid, induce messages (also called signals) in the cells. They are hence key regulators of cell signalling. In the animals of higher order, such as Humans, PI3Ks come in different flavours. In particular, the PI3Ka and PI3Kβ work in concert to orchestrate key cellular and organismal process, such as cell migration, proliferation in one hand, or formation of vascular and lymphatic vessels, regulation of glycemia and other metabolic processes, control of organ organisation, growth and renewal, fertility, immune reactions and thrombosis on other hand. Hence, their dysregulation leads to several disease, such as cancer, diabetes, inflammatory disease and overgrowth syndromes. Here, we review the progress made by our scientific community in the last 15 years to understand and target those proteins.Small molecule inhibitors that inhibit those proteins are already used to treat patients with breast cancer. Novel applications based on the knowledge gathered are coming.
This work on PI3K isoforms has led to 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 :
- Cell Signalling,
- Cancer,
- Oncogenic signalling,
- Tumor suppressor,
- PI3K/AKTmTOR
Collaboration and thanks
« JGG’s lab was/is funded by ARC (PJA20171206596), Toucan ANR Laboratory of Excellence, MSCA-ITN/ETN PhD-PI3K (Project ID: 675392, salary to SA, FRD), Fondation de France (French Foundation) (salary to BT), GSO, Fondation Toulouse Cancer Santé (Toulouse Cancer Health Foundation), Regeneve (Région Midi-Pyrénées/FEDER), ANR-JCJC RADIANCE (salary to BT), Ligue Nationale Régionale contre le Cancer (French National Anti-Cancer League) (funds and salary to CC), Fonroga Prize (CC) and Inca Plan Cancer. »
Contact :
Julie Guillermet-Guibert PhD
Team CRCT : SigDYN : Intégration des signaux cellulaires & PI3K de classe I, II, III.
Mail : julie.guillermet@inserm.fr
One picture
Roles of PI3Kalpha and PI3Kβ in organism
