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.