Energy sensor a potential target for future cancer drugs

An energy sensing enzyme can potentially become a therapeutic target for future cancer drugs as it is responsible for sensing the available supply of GTP -- an energy source that fuels the uncontrolled growth of cancer cells, new research has found.

An international study team formed by a University of Cincinnati (UC) cancer researcher found that the enzyme PI5P4Kß (phosphatidylinositol-5-phosphate 4-kinase-ß) acts like the arrow on a fuel gauge.

The enzyme senses and communicates (signals), via a second messenger, the amount of GTP fuel that is available to a cell at any given time. Until now, the molecular identity of a GTP sensor has remained unknown, a University of Cincinnati Academic Health Centre statement said.

Energy sensing is vital to the successful proliferation of cancer cells. A large amount of GTP is required in rapidly dividing cells, and cells need to know that the fuel is available to them.

GTP - guanosine triphosphate - is one of two energy molecules used by cells. The other is ATP (adenosine triphosphate).

ATP handles the bulk of a cell's energy requirements, while GTP is required for protein synthesis and is a signalling molecule that helps direct processes within the cell.

When GTP levels are increased and utilised as fuel by rampaging cancer cells, its ability to perform its primary goals is compromised.

"If we can interfere with the ability of PI5P4Kß to sense fuel availability and communicate that information, we may be able to slow or halt the growth of cancers, including the aggressive brain cancer glioblastoma multiforme and cancers that have metastasised to the brain," said Atsuo Sasaki, an assistant professor in the Division of Hematology Oncology at the UC College of Medicine.

Initially, Sasaki and his team faced scepticism regarding the existence of GTP energy-sensing. However, with a pilot grant funded by Cincinnati's Walk Ahead for a Brain Tumour Cure and other local sources, the researchers were able to pursue their study and acquire enough promising data to earn a five-year, $1.67 million grant from the National Institutes of Health in 2014.

Sasaki, also a researcher at the Brain Tumour Centre at the UC Neuroscience Institute and UC Cancer Institute, teamed up with Toshiya Senda, a professor at the High Energy Accelerator Research Organisation in Tsukuba, Japan, for the study.

Their findings were published recently in the journal Molecular Cell.