Institut National De La Sante Et De La Recherche Medicale

Université Paul Sabatier (Toulouse III)

Centre National De La Recherche Scientifique

Cnrs

Klinikum Rechts Der Isar Der Technischen Universitat München

Julie Guillermet-Guibert

Célia Cintas

Emmanuelle Mouton-barbosa

Odile Schiltz

Maximillian Reichert

Thibaut Douche

Marie-Pierre Bousquet

PI3K signalling is the most increased pathway in human cancers. The four isoforms of PI3K are thought to be activated by different redundant mechanisms leading to a common downstream signalling. However, the mutational pattern of PI3K pathway or its level of expression is not sufficient to predict the sensitivity to PI3K inhibitors. By identifying for the first time a phosphopeptide that predict the sensitivity to p110α and/or p110γ inhibitors, the inventors provide insight in how to handle heterogeneity of PI3K expression patterns in tumoral samples for the choice of available PI3K-targetting drugs. Accordingly, the present relates to a phosphopeptide characterized by the amino acid sequence as set forth in SEQ ID NO:1 (PGPSDHQSQEASQFER) wherein the threonine residue at position 3 is phosphorylated.

Marker for predicting the sensitivity to PI3K inhibitors

PI3K signalling is the most increased pathway in human cancers. The four isoforms of PI3K are thought to be activated by different redundant mechanisms leading to a common downstream signalling. The inventors questioned this concept, by mapping differential isoform-specific downstream signalling in response to their constant selective inhibition in pancreatic cancer, a disease currently without therapy. They identified common and specific signals activated by each PI3K isoform. These data make the rational for the development of highly selective PI3K isoform drugs used in combination, instead of compounds inhibiting all PI3Ks. In particular, the inventors showed that combined p110a and 110&#x3b3; inhibition is the most efficient strategy for pancreatic cancer patients.

Combination treatment of pancreatic cancer

Growing community of inventors

Toulouse, France

Julie Guillermet-Guibert