Cancer cells (shown here) need to produce energy in their nucleus in order to spread. But new research found a way to prevent them from doing so.
These hormones help the breast cancer to spread, so hormone therapy aims to prevent cancer from spreading or recurring by blocking the hormone receptors.
However, these hormone-blocking drugs often have a wide array of side effects or are not fully effective because the cancer finds new ways to spread or becomes resistant to treatment.
But now, new research — carried out by scientists from the Karolinska Institutet and Science for Life Laboratory in Solna, Sweden — offers new hope, as the team discovered a way to starve hormone-fueled breast cancer cells of energy. This may lead to better drugs in the future.
The researchers — led by Prof. Thomas Helleday, of the Department of Medical Biochemistry and Biophysics in the Karolinska Institutet — found a protein that helps breast cancer cells to get the energy they need to proliferate. They also found a compound that inhibits this protein.
Brent D.G. Page and Nicholas C.K. Valerie, of the Science for Life Laboratory at Karolinska, are the first authors of the new study, which was published in the journal Nature Communications.
Starving breast cancer cells of energy
Prof. Helleday and his colleagues originally set out to investigate the role of the so-called NUDT5 protein — a nucleotide-metabolizing enzyme — in breast cancer.
They discovered that NUDT5 is used by breast cancer cells to create energy in their nucleus. The nuclear energy thus created is used to drive cancer-causing gene expression.
So, the researchers shifted their focus to developing a molecule that could block NUDT5's activity.
This compound is called TH5427, and laboratory experiments revealed that it successfully acts as an NUDT5 inhibitor, stopping the spread of breast cancer cells.
The authors summarize their findings, saying, "Utilizing these state-of-the-art techniques led us to discover TH5427, a potent and cell-active NUDT5 inhibitor that can be used to further understand the role of NUDT5 in biological systems."
"We have provided a proof of concept showing that TH5427 blocks NUDT5-dependent processes in breast cancer cells, and targeting NUDT5 may represent a promising new therapeutic approach for breast cancer treatment," explain the researchers.
Beyond this "proof of concept," the scientists now hope to discover and develop more NUDT5 inhibitors, which, in the long run, could help to drastically improve the lives of breast cancer patients. They say:
"Ongoing efforts are aimed at formulating NUDT5 inhibitors for in vivo use and will focus on further investigating the role of NUDT5 in cancer and other disease models."
Ultimately, Prof. Helleday and his colleagues hope to be moving toward human clinical trials, but the study's senior author emphasizes the long road ahead.
"They're exciting findings, but the path ahead is long since we still know very little about how NUDT5 operates," he says.
The researchers hope that their findings will help to treat not only breast cancer, but hopefully other forms of cancer, as well.