Novel BRAF Inhibitors

In 2002 the ICR began a drug discovery programme funded by The Wellcome Trust, to develop novel inhibitors of the enzyme BRAF, mutations in the B-RAF gene that codes for this enzyme are found in 7 per cent of human cancers, including some colorectal, ovarian and thyroid cancers.

The presence of mutated BRAF in such a high proportion of melanoma cases and in such a wide range of human cancers, led researchers to examine the protein as a target for anticancer therapy.

A team led Professor Caroline Springer of the Cancer Research-UK Centre for Cancer Therapeutics and Professor Richard Marais of Cancer Research-UK Centre for Cell and Molecular Biology have discovered four novel series of compounds that are potent BRAF inhibitors. These compounds have been shown to be orally active in a number of xenograft models and three lead pre-clinical candidates have now been selected. 

The production of therapeutics that are targeted to specific mutated proteins will ultimately mean that doctors are better placed to tailor treatment to the individual patient. If a BRAF mutation is found in a patient, then a BRAF inhibitor could be employed. If, on the other hand, no BRAF mutation is detected, the patient could be spared drugs that likely would not help them.

The drug discovery approach Professors Springer and Marais are taking is based on high-throughput screens: large-scale, automated sets of experiments that test series of compounds at a time for each compound's ability to block the activity of BRAF.

The Wellcome Trust are now actively looking for a commercial partner to licence these compounds.