Main Menu

Discovering and developing a leading PI3K inhibitor

We discovered and helped develop one of the very first in a new class of PI3 kinase inhibitors.

Sample Test Tubes

The drug, known as pictilisb (previously GDC-0941), was discovered by the Cancer Research UK Cancer Therapeutics Unit here at The Institute of Cancer Research, London and its collaborators.

It is now showing promising activity in the clinic, including in trials run at the Drug Development Unit at the ICR and The Royal Marsden NHS Foundation Trust.

PI3 kinase is a lipid signalling enzyme which plays a key role in the development and progression of many cancers as a result of a variety of cancer-causing molecular abnormalities. We’ve seen promising responses with pictilisib in several cancer types, including breast and ovarian, myeloma, melanoma and a rare type of gastrointestinal cancer.

More potential

There are also signs that the drug could work particularly well in combination with other new targeted treatments which interfere with other components in the PI3 kinase signalling network – especially anti-hormone therapies for oestrogen receptor and progesterone receptor positive breast cancers. It is showing particularly positive results in a combination trial with the drug fulvestrant which blocks oestrogen receptors.

The pictilisib story began with a collaboration between molecular biologists, Professor Mike Waterfield (Ludwig Institute for Cancer Research, UCL) and Professor Peter Parker (then at the Cancer Research UK London Research Institute) who teamed up with drug discoverers Professor Paul Workman and Dr Flo Raynaud at the ICR to develop inhibitors of PI3 kinase.

Working initially with the Japanese pharma company Yamanouchi (now Astellas), the team discovered potent and selective inhibitors.

Professors Workman, Waterfield and Parker then formed the biotech company Piramed Pharma which worked closely with the Cancer Research UK Cancer Therapeutics Unit at the ICR to discover pictilisib.

The company licenced its PI3 kinase inhibitors to the top biotech company Genentech for use in cancer, and in 2008, Piramed was acquired by Roche to develop the inhibitors for inflammatory diseases. Partnering with Genentech provided the resources to take the drug into early clinical trials – one of which was led by Professor Johann de Bono of the Drug Development Unit of the ICR and The Royal Marsden – and then into phase II studies in breast and other cancers.

Leading to further research

The research has also fed back into the laboratory, where PI3 kinase inhibitors from the collaborative research are being used to help us further understand what PI3 kinase does in the cell, and how things go wrong in cancer.

By making these available to scientists around the world as a tool compound, our work has enabled the discovery of further drugs and drug combinations targeting PI3 kinase signalling.

In 2012, Professor Workman, then Director of the Cancer Research UK Therapeutics Unit and now the ICR’s Chief Executive, was named ‘Entrepreneur of the Year’ by the Royal Society of Chemistry, recognising his effort and skill in ensuring new treatments like pictilisib make their way from bench to bedside without delay.

A publication about pictilisib from Professor Workman and Dr Reynaud was one of 16 studies selected by the American Association of Cancer Research journal Molecular Cancer Therapeutics as having the greatest impact on patients.