For the first time, a single molecule has been identified that could be the central to the mechanism of spread by prostate cancer.
The study is completed by researchers from the Thomas Jefferson University in Philadelphia, PA and is published in the journal Cancer Cell.
The results of the study offer a target for the development of a drug that may prevent metastasis (spreading growth) in prostate cancer – and maybe other cancers as well.
Karen Knudsen, PhD, director of the Sidney Kimmel Cancer Center at Thomas Jefferson University says:
“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.”
Dr. Knudsen adds: “These results strongly suggest DNA-PKcs is a master regulator of the pathways and signals that lead to the development of metastases in prostate cancer, and that high levels of DNA-PKcs could predict which early stage tumors may go on to metastasize.”
Tumors go through a number of DNA mutations which makes its cells more mobile, able to enter bloodstream and stick to a new location to form a new lump.
Dr. Knudsen and team have shown that DNA-PKcs molecule appears to be central to many of the processes required for a cancer to spread.
The DNA repair kinase rejoins broken/mutated DNA strands in a cancer cell, acting as glue to many broken pieces of DNA and keeping alive a cell which should normally self-destruct.
Other studies have showed the role of DNA-PKcs in resistance to prostate cancer treatment but may have other huge roles in cancer. Specifically, the researchers found that DNA-PKcs modulates the Rho/Rac enzyme, which allows many cancer cell types to become mobile, as well as a number of other steps.
The team also worked in mice as mock-ups of human prostate cancer.
sing agents that suppress DNA-PKcs production or function, the researchers could block the development of metastases.
In mice with aggressive human tumors, an inhibitor of DNA-PKcs also reduced the overall tumor burden in distant sites of cancer spread.
Dr. Knudsen and team then analyzed DNA-PKcs in human disease through 232 samples taken from prostate cancer patients.
They analyzed the amount of DNA-PKcs in cells and made a comparison with medical records. A spike in the kinase levels was a strong predictor of cancer spread and poorer prostate cancer prognosis.
DNA-PKcs was also found to be much more active in human samples of castrate-resistant prostate cancer, an aggressive and treatment-resistant form of the disease.
Pharmaceutical development under way
A drug has already been developed that inhibits DNA-PKcs – it is being tested in early clinical trials. Dr. Knudsen explains:
“We are enthusiastic about the next step of clinical assessment for testing DNA-PKcs inhibitors in the clinic. A new trial will commence shortly using the Celgene CC-115 DNA-PKcs inhibitor.
“Although the pathway to drug approval can take many years, this new trial will provide some insight into the effect of DNAP-PKcs inhibitors as antitumor agents.
“In parallel, using this kinase as a marker of severe disease may also help identify patients whose tumors will develop into aggressive metastatic disease, so that we can treat them with more aggressive therapy earlier.
“Given the role of DNA-PKcs in DNA repair as well as control of tumor metastasis, there will be challenges in clinical implementation, but this discovery unveils new opportunities for preventing or treating advanced disease.”
Copyright: Medical News Today from article http://www.medicalnewstoday.com/articles/296654.php