Abstract: 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 p110? and/or p110? 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 (PGTPSDHQSQEASQFER) wherein the threonine residue at position 3 is phosphorylated.

Abstract: The molecular determinants of chronic pancreatitis leading to pancreatic cancer are underexplored. Genetic or pharmacological inactivation of signaling enzyme PBKa prevents pancreatic fibroinflammatory reaction, while increasing its regenerative capacities, which makes PBKa inhibitors an anti-cancer prevention dmg for these patients. Thus the present invention relates to a method for the prophylactic treatment of cancer in a patient suffering from pancreatitis comprising administering to the patient a therapeutically effective amount of a PBKa- selective inhibitor.

Abstract: Rapid, easy and early pancreatic cancer diagnosis and therapeutic follow up continue to necessitate an increasing attention towards the development of effective treatment strategies for this lethal disease. The non-invasive quantitative assessment of pancreatic heterogeneity is limited. Here, the inventors report the development of a preclinical imaging protocol using ultrasonography and shear wave technology in an experimental in situ pancreatic cancer model to measure the evolution of pancreatic rigidity. The inventors evaluated the feasiblity of a live imaging protocol by assessing pancreas evolution with Aixplorer technology across 37 weeks. Protumorigenic mutations induced a significant decrease of the rigidity of pancreatic tissue before tumors developed in correlation with the detection of senescent marker p16-positive cells. Thus the promising results indicate the potential of the shear wave elastography to support individualization of diagnosis in this most aggressive disease.

Abstract: 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? inhibition is the most efficient strategy for pancreatic cancer patients.

Abstract: 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? inhibition is the most efficient strategy for pancreatic cancer patients.

Abstract: 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 p110? and/or p110? 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 (PGTPSDHQSQEASQFER) wherein the threonine residue at position 3 is phosphorylated.