Discovering the "switch" that helps cancer metastasize

LFor the first time, scientists have identified a key molecule that helps cancer spread to other parts of the body, paving the way for new cancer treatments.

The molecule DNA-PKcs has been found to play a key role in triggering cancerous tumors to metastasize throughout the body. Illustration: Corbis

Cancer is a disease that depends on cell growth. In most cases, tumors only become deadly once they have metastasized, or spread, from their original location to other parts of the body.

Researchers from Thomas Jefferson University (USA) now claim that they have discovered a single molecule that appears to be the "key factor" that promotes metastasis in prostate cancer.

"Finding a way to stop or prevent cancer metastasis has proven difficult," said Karen Knudsen, MD, professor of urology, a member of the research team. "We found that a molecule called DNA-PKcs may provide a means to shut down key growth pathways, controlling metastasis before it starts."

Metastasis is considered the final stage of cancer. The tumor undergoes a series of changes in its DNA—mutations—that make the cells more mobile, allowing them to enter the bloodstream. The cells also become more “sticky,” which helps them anchor themselves to new sites, such as the bones, lungs, liver, or brain.

The pathways that lead to metastasis are complex, involving many different biochemical pathways, but new research suggests that a single molecule lies at the root of many of them. That molecule is DNA-PKcs, a DNA repair kinase.

Kinases are a class of enzymes that specialize in rejoining broken or mutated DNA strands in a cancer cell, acting as glue for multiple broken pieces of DNA, thus sustaining the life of a cell that would normally self-destruct.

Previous studies have shown that DNA-PKcs is involved in treatment resistance in prostate cancer, in part because it repairs damage that often threatens tumor survival, caused by radiation and other treatments.

In the new study, Professor Knudsen and colleagues discovered that DNA-PKcs also has other, more far-reaching roles in cancer: it serves as a key coordinator of a network that activates a whole range of metastatic processes. In particular, DNA-PKcs modulates another enzyme that allows many cancer cells to become mobile, as well as facilitating other key processes such as cell migration and invasion.

Through experiments in mice with human prostate cancer, Dr. Knudsen's team demonstrated that they could disable metastasis of malignant tumors by using factors that inhibit the production or function of DNA-PKcs. In addition, the DNA-PKcs inhibitor also reduced the overall tumor size at metastatic sites.

When analyzing samples from prostate cancer patients, the team also found that increased levels of the DNA-PKcs kinase were a strong predictor of developing metastatic processes and poor treatment outcomes.

The researchers hope the new discovery will help them achieve their goal of developing a drug that can stop prostate cancer tumors from spreading. The team also hopes that the discovery will eventually pave the way for new effective treatments for other types of cancer.

According to vietnamnet