New mechanisms of PI3K-driven cancer development and alternative uses of PI3K-inhibitors in cancer

The PI3K/PTEN signalling axis is one of the most frequently aberrantly-activated pathways in cancer. PTEN is a tumour suppressor gene, the loss of which leads to PI3K-pathway over-activation.

PI3K-inhibitors have not been effective as anti-cancer agents in the clinic, with the exception of the approved PI3Kδ-inhibitors for B-cell malignancies. This indicates the need to better understand the mechanisms by which sustained, low-level PI3K-activation leads to cancer and to explore alternative ways to use PI3K-inhibitors in the clinic beyond their use as potential direct anti-cancer-cell cytotoxics/cytostatics used at the maximum-tolerated dose.

The project objectives are: (1) to investigate the possible contribution of sustained PI3K-driven leukocyte expansion/inflammation in cancer predisposition, and (2) to explore alternative uses of clinical-stage PI3K-inhibitors in cancer prevention and cancer immunotherapy. For these studies, we will use a genetic mouse model that faithfully reflects a human PI3K-driven cancer predisposition syndrome, called PTEN hamartoma tumour syndrome (PHTS). PHTS patients carry germline inactivating PTEN mutations and are predisposed to cancer.

This is a basic science project with strong translational potential that covers immunology / signalling / cell biology and pre-clinical drug studies, based on solid unpublished evidence from the host laboratory. It involves interactions with PTHS patients and with pharma.

More detailed information about the research project is available on request [Email Address Removed]