Biomarkers for particularly aggressive prostate cancers discovered
By ANITuesday, July 13, 2010
WASHINGTON - Researchers have uncovered a mechanism that determines prostate cancer aggressiveness, providing new targets for diagnosis and treatment.
The study, led by Ze’ev Ronai, at Sanford-Burnham Medical Research Institute (Sanford-Burnham), appears in the journal Cancer Cell.
The research uncovers a protein named Siah2, which initiates a cascade of molecular events that turn a non-malignant tumour into a metastatic neuroendocrine tumour.
Dr. Ronai, associate director of Sanford-Burnham’s National Cancer Institute-designated Cancer Center, said: “In identifying this protein pathway, which determines the formation of neuroendocrine tumors, we’ve identified new markers that can be used to distinguish the dangerous cells and find new targets for therapy.”
In collaboration with four other medical centres across the US, Dr. Ronai and his colleagues analyzed human prostate cancer samples and found that Siah2 and the other proteins it triggers is detected more often in the aggressive neuroendocrine forms of prostate tumors than in other types. By acting as markers for particularly aggressive prostate cancers, Siah2 and its partners could provide doctors with an early warning sign for tumors that are likely to metastasize.
To further validate these findings, the Siah2 gene was inactivated in mice already prone to developing aggressive prostate tumors. Although benign growths still appeared, they failed to develop into neuroendocrine tumors.
First author Jianfei Qi, postdoctoral researcher in Dr. Ronai’s laboratory, said: “When we inhibit the Siah2 pathway in mice, we eliminate the neuroendocrine-type cells from the prostate tumours. Since prostate cancers containing neuroendocrine-type cells are resistant to current therapies, we are pleased to find that targeting Siah2 might provide an alternate approach to treating this disease.”
Members of the Sanford-Burnham research team are now looking for chemical compounds that inhibit the activity of Siah2 or other proteins along the chain.
They hope to find a new drug that will block the series of molecular events leading to the formation of neuroendocrine-type cancer cells, thus keeping prostate tumors in check. (ANI)
