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UCL Cancer Institute

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Cell Signalling Research Group

Group Leader: Professor Bart Vanhaesebroeck, PhD FMedSci

PI 3-kinases (PI3Ks) are signal transduction enzymes that are involved in several human diseases including cancer, overgrowth syndromes, inflammation and auto-immunity. Drugs to block PI3K action are being developed by the pharmaceutical industry. Our work has led to the first approved PI3K inhibitor (2014), for the treatment of human B-cell lymphomas. This medicine is currently also being tested in cancer immunotherapy of solid tumours.

We welcome informal enquiries - if you would like to work with us, please contact Bart Vanhaesebroeck bart.vanh@ucl.ac.uk .

PI3K in disease…

Our laboratory covers 3 main lines of research:

1. PI3K isoform function: we aim to uncover the functions of the PI3K family members in normal physiology and in disease, and to understand their molecular mechanism of action. The main sponsors of this work are Cancer Research UK, the EU and the BBSRC.

PI3K isoforms with PTEN

2. PTEN Hamartoma Tumour Syndrome (PHTS): this is a human condition in which the PTEN gene is faulty, predisposing to overgrowth, autism-like spectrum and cancer. PTEN is an enzyme which keeps PI3K in check. We aim to understand how PTEN works in an organism, and to explore if PI3K inhibitors can be used to alleviate PHTS. The main sponsor of these studies is the PTEN Research Foundation.

3. Exploring alternative ways to interfere with PI3K signalling: this is a drug development programme, under the umbrella of the BRC Therapeutic Innovation Network (TIN). Bart V. is the co-Chair of the Small Molecule Therapeutic Innovation Network (TIN), launched in July 2018. The main sponsors of this work are UCL and the NIHR University College London Hospitals Biomedical Research Centre.

A highlight of our work to date is the discovery of PI3Kdelta, a PI3K family member that is highly expressed in white blood cells, as a drug target in various diseases. Our team has been involved in the characterization of PI3Kdelta ‘all the way’, from gene cloning through to the generation of the first mouse models and the development of PI3Kdelta inhibitors (by PIramed UK, acquired by Roche in 2008). Over the years, we have uncovered PI3Kdelta as a drug target in immunity, inflammation and haematological cancers and, most recently, as a target for cancer immunotherapy.

In 2014, a PI3Kdelta inhibitor (idelalisib from Gilead Sciences) was the first PI3K inhibitor to be approved, namely for the treatment of specific blood cancers. PI3Kdelta inhibitors are also being trialled in airway inflammation and in the 'Activated PI3Kdelta Syndrome' (APDS), a disease due to activing mutations in the PI3Kdelta gene. Based on our recent finding that PI3Kdelta inhibition leads to the activation of the immune system against cancer (Nature 2016:535:580), PI3K delta inhibitors are now also being tested in cancer immunotherapy trials in solid tumours.


Publications

View full list of publications on PubMed