Cancer-causing enzyme could be stopped

Scientists from the MRC's Laboratory of Molecular Biology (LMB) and the Albert Einstein College of Medicine have discovered a way to stop an enzyme responsible for many cancers.

They've worked out a new way to target the enzyme – PI3K - that plays a role in the uncontrollable division of cells. The scientists found that the mutation of PI3K could be stopped by more specifically targeting the part of the enzyme responsible for the change.

Cancers occur when cells begin to reproduce uncontrollably. This starts in a single cell, a stage called initiation, and then spreads as the mutant cell divides carrying the original mutation, and often adopting others.

Scientists from around the world are looking to unravel what happens in the very initial stages of cancer to find out how to stop cells developing mutations and how to better target those cancerous cells that have mutated at very early stages.

One known cause of cell disruption is the mutation of an enzyme called phosphoinositide 3-Kinase or PI3K. The misbehaviour of this enzyme is thought to be responsible for a quarter of all cancers.

So far scientists' attention had largely been focused on a site in the enzyme that produces a chemical message. But the latest research led by Dr Roger Williams at the Medical Research Council's LMB together with Jonathan Backer at the Albert Einstein College of Medicine and published in Science has found a different way to inhibit PI3K cancer-causing mutations earlier in the process.

Dr Williams explained: "The PI3K enzyme plays a key role in controlling how human cells behave and its mutation can lead to numerous types of cancers. But before the enzyme is active, it has to release a partner protein that acts as a molecular brake. We developed a three-dimensional model for how this brake is applied. We then made a mutated partner protein that acts as a brake only for the cancer-causing enzyme. This intervention may be able to stop a cancerous cell from dividing uncontrollably."

Dr Williams added "PI3K is already a well known target for cancer drug development. We hope this extra insight into the enzyme's structure and where cancer-causing mutations occur will help those in drug development create better designed drugs to tackle cancer. Reversing cancer at very early stages would obviously be of huge benefit to patients, but implies the early identification of cancers."