Scientists find a way to stop the spread of cancer cells
A molecule described as the "lynchpin" of cancer spread has been identified, paving the way to potentially life-saving treatments.
Targeting the protein DNA-PKcs could prevent the deadly spread of prostate cancer and possibly other cancers as well, scientists believe.
Metastasis, the migration of tumours away from their original site to vital organs such as the liver and brain, is usually what causes cancer to kill.
US lead scientist Dr Karen Knudsen, director of the Sidney Kimmel Cancer Centre at Thomas Jefferson University in Philadelphia, said: "Finding a way to halt or prevent cancer metastasis has proven elusive. We discovered that a molecule called DNA-PKcs could give us a means of knocking out major pathways that control metastasis before it begins."
Before cancer spreads, tumours develop DNA mutations that make their cells more mobile and able to enter the bloodstream. The cells also become "sticky", which helps them anchor into new locations such as the bone, lungs, liver or brain.
The processes by which this happens are complex, involving many different biological pathways - but the new research suggests that just one molecule, DNA-PKcs, lies at the root of many of them.
The molecule is a type of enzyme known as a "repair kinase" that fixes broken or mutated DNA strands in cancer cells. Because of DNA-PKcs, defective cells that should normally self-destruct are kept alive.
Previous research has shown that the molecule helps drive treatment-resistance in prostate cancer by repairing damage to tumours caused by radiation and other therapies.
Dr Knudsen's team found that DNA-PKcs also seems to act as a master regulator of signalling networks that turn on the whole metastatic process.
It has effects that enable many cancer cell types to become mobile, and is involved in other pathways responsible for cell migration and invasion.
In mice with human prostate cancer, blocking DNA-PKcs prevented the spread of tumours. Cancer growth in metastatic sites was reduced in animals with aggressive human tumours.
Further analysis of tissue samples from 232 prostate cancer patients revealed that spikes in kinase levels strongly predicted metastasis and poor outcomes.
DNA-PKcs was much more active in men with prostate cancer who had ceased to respond to hormone therapy.
A drug that inhibits DNA-PKcs, made by the pharmaceutical company Celgene, is now being tested on patients with advanced solid tumours and leukaemia in an early-stage Phase 1 clinical trial. The drug is code-named CC-115.