Researchers say they've identified a molecule that acts as the "linchpin" that drives the deadly spread of many cancers, a discovery that could lead to new effective treatments of cancer.
The protein molecule, known as DNA-PKcs, is what helps a cancer spread from the site of the original tumor and is critical in the movement of cancer cells around the body, they say.
Experiments with mice given the human form of prostate cancer suggest targeting that molecule could prevent such "metastatic" spread in humans to vital organs, which is often the cause of death in cancer patients, researchers at Thomas Jefferson University in Philadelphia report.
"Finding a way to halt or prevent cancer metastasis has proven elusive," says researcher Karen Knudsen of the university's Sidney Kimmel Cancer Center. "We discovered that a molecule called DNA-PKcs could give us a means of knocking out major pathways that control metastasis before it begins."
Considered the last stage of cancer, metastasis involves mutations in the DNA of tumor cells that cause them to become more mobile and capable of moving through a patient's bloodstream, then turn "sticky" and attach themselves to bone or vital organs as the beginnings of new tumors, the researchers explain.
DNA-PKcs repairs and rejoins cancer cells' mutated or broken DNA strands, bringing together broken bits of DNA so that cells that would under normal circumstances self-destruct are kept alive.
It also apparently serves as a regulator of biological signaling networks to initiate the entire process of metastasizing, the researchers report in their study appearing in the journal Cancer Cell.
An analysis of more than 200 samples taken from patients with prostate cancer examining the level of DNA-PKcs contained in cancer cells found that an increase in the levels served as a strong predictor of subsequent metastases and likely poor outcomes for the cancer, they reported.
"The finding that DNA-PKcs is a likely driver of lethal disease states was unexpected, and the discovery was made possible by key collaborations across academia and industry," says Knudsen, citing research input from the University of Michigan, UCLA, Columbia University, the Cleveland Clinic, the Mayo Clinic and the gene research firm GenomeDX.
One company is already developing a drug that can inhibit the activity of DNA-PKcs and has initiated a phase 1 study, Knudsen says.
"We are enthusiastic about the next step of clinical assessment for testing DNA-PKcs inhibitors in the clinic,' she says.
"Although the pathway to drug approval can take many years, this new trial will provide some insight into the effect of DNA-PKcs inhibitors as anti-tumor agents."
