Researchers root out Possible Trigger to Destroy Cancer

Melbourne investigators have identified a new way of causing cell death, in a finding that could result in medicines to deal with cancer and autoimmune disease.

Programmed cell death, also known as apoptosis, is a natural approach that eliminates unwanted cells from the body. Failing of apoptosis can enable cancer cells to develop unchecked or immune cells to inappropriately attack the body.

The protein well-known as Bak is central to apoptosis. In healthy cells, Bak sits in an inert state but when a cell gets a signal to die, Bak changes into a killer protein that damages the cell.

Institute investigators Dr Sweta Iyer, Dr Ruth Kluck and colleagues have identified a new way of directly initiating Bak to induce cell death. Their results are recently presented in the journal Nature Communications.

The investigators identified that an antibody they had generated to study Bak basically bound to the Bak protein and activated its activation.

Commenting on their research Dr Kluck stated

The results were absolutely unexpected, we were thrilled when we noticed we had identified a completely new way of triggering Bak. She hope to use this finding to develop medicines that promote cell death.

There is great attention in developing medicines that lead to Bak activation to treat conditions such as cancer where apoptosis has gone awry. This finding provides us a new beginning point for developing treatments that directly stimulate Bak and cause cell death.

The investigators used info about Bak’s three-dimensional structure to figure out accurately how the antibody activated Bak.

“It is well identified that Bak can be triggered by a class of proteins known as ‘BH3-only proteins’ that combine to a groove on Bak. We were amazed to discover that despite our antibody binding to a absolutely distinct site on Bak, it could still induce activation.

Drugs that targeted this new activation site could be helpful in combination with other treatments that promote cell death by resembling the BH3-only proteins.

“The benefits of our antibody is that it cannot be ‘mopped up’ and neutralised by pro-survival proteins in the cell, possibly decreasing the possibility of drug resistance developing.

The investigators are now working with collaborators to develop their antibody into a drug that can gain access to Bak inside cells.

The study was backed by the National Health and Medical Research Council, the Australian Research Council, the Victorian State Government Operational Infrastructure Support Scheme and the Victorian Life Science Computation Initiative.