Research at the University of Michigan’s (UM) Comprehensive Cancer Center, performed by pathologist Arul Chinnaiyan, MD, PhD, is currently focused on devising new diagnostics that will improve, or be used in conjunction with, current prostate cancer detection methods. New findings by Dr. Chinnaiyan and his group link small molecule metabolites to prostate cancer. A number of these metabolites may soon lead to a non-invasive urine test for early detection of the disease.
“Generally speaking, we are looking to develop a set of biomarkers that can predict more aggressive forms of prostate cancer through the urine or blood,” said Dr. Chinnaiyan, director of the Michigan Center of Translational Pathology and S.P. Hicks Endowed Professor of Pathology at UM Medical School and two-time PCF Competitive Award recipient. “Studying metabolites allows us to take a holistic picture of the molecular alterations that occur in prostate cancer.”
Determining biomarkers for the purpose of differentiating more indolent (less threatening) prostate cancers from those with more aggressive or lethal properties will help to improve selection of patients that may benefit from early radical therapies such as surgery or radiation. The current PSA test is ineffective for identifying aggressive prostate cancers - resulting in potential over-diagnosis and over-treatment of prostate cancer.
Until new tests are widely available, most patients with low grade prostate cancer may continue to receive immediate aggressive therapy.
According to Dr. Chinnaiyan, having advanced indicators that will differentiate the two variances of cancer would give physicians valuable clues as to which patients need aggressive treatment.
“When a man gets diagnosed with prostate cancer the physician often doesn’t know whether that version of prostate cancer is going to metastasize and actually kill the patient or if it is a more prevalent prostate cancer which is slow growing,” said. Dr. Chinnaiyan. “Since we can’t now tell the difference we end up essentially overtreating the patient by removing the prostate or giving radiation treatment regardless of the type of prostate cancer that particular patient may have.”
Metabolites & Prostate Cancer
Encouraging data resulting from metabolite profiling of urine and prostate tissue from prostate cancer patients was published by Drs. Chinnaiyan, Sreekumar, and colleagues in February’s edition of the scientific journal, Nature. Sarcosine, one of the metabolites, was elevated in specimens from patients with metastatic prostate cancer.
“There has been a considerable amount of work done looking at gene and proteins in cancer specimens, and in this particular study we extended that further by looking at these small molecules to analyze different stages of prostate cancer progression,” explains Dr. Chinnaiyan.
“Essentially, by studying metabolites we were looking for a more complete picture of the types of molecular alterations that can occur in prostate cancer. Metabolomics, the massively parallell study of all metabolities in biological specimens, allows us to look very deeply at some of the functions of the cells and the biochemistry that occurs during cancer development.”
During Dr. Chinnaiyan’s four-year study of metabolites and their connection to prostate cancer, he and his group profiled more than 1,000 metabolites in tissue, blood and urine specimens associated with benign, early stage, and advanced prostate cancer. Sarcosine was elevated in most metastatic prostate cancer samples studied.
Furthermore, and of great interest, is the fact that in laboratory studies, the addition of sarcosine to cultured benign prostatic cells transformed them into an invasive form of prostate cancer.
“We were certainly pleased to discover that sarcosine was associated in the urine specimens from men with prostate cancer. It was a suprising finding,” said Dr. Chinnaiyan.
More research is needed by Dr. Chinnaiyan’s group to fully examine and understand the role sarcosine plays in prostate cancer progression. Moreover, Dr. Chinnaiyan looks to study other metabolites as nine additional ones were shown to be present in prostate cancer as well.
“The long term goal is to have a systems perspective of the types of molecular alterations that go wrong in prostate cancer progression,” said Dr. Chinnaiyan. “We want to take advantage of metabolites as potential tools for developing new therapeutic targets. Our end goal is to create panels of different metabolites - not just a single one – to provide better diagnosis and prognosis of prostate and other human tumors.”
Recent findings out of the University of Michigan have linked metabolites to the occurrence of prostate cancer. This research, spearheaded by PCF-funded investigator, Dr. Arul Chinnaiyan, and his colleague Dr. Arun Sreekumar (currently of the Medical College of Georgia), may one day allow medical practitioners the ability to administer a simple urine test for detecting aggressive forms of prostate cancer.