Prostate cancer is almost harmless. Sometimes.
At nearly 200,000 cases diagnosed annually in the U.S., prostate cancer is the second most common cancer (after skin cancers) in men. The cancer often grows slowly – in fact, in older men diagnosed with the disease, watchful waiting is sometimes the best treatment option. But some prostate cancers are more aggressive. The question is, which ones?
"One of the main clinical issues in prostate cancer is trying to distinguishing aggressive prostate cancer that goes on to metastasis, versus the indolent or slow-growing version of the disease," Arul Chinnaiyan told reporters at a press conference earlier this week. And as a result, physicians "often end up overtreating because we cannot distinguish between aggressive and indolent disease."
At the press conference, Chinnaiyan was describing sarcosine, an amino acid that could serve as a biomarker to separate aggressive from indolent cancers. And sarcosine could be a therapeutic target as well. Co-author John Wei said, "Therapeutically, you could envision a small molecule or antibodies that might inhibit some of the pathways that lead to sarcosine elevation."
Sarcosine was identified by a team from the University of Michigan (Ann Arbor), Pennsylvania State University (State College), and Metabolon (Durham, North Carolina). Their results appear in the Feb 12 issue of Nature.
At the press conference, co-author Christopher Beecher said that the study "marks the coming of age of the science of metabolomics," or the study of metabolic pathways in their entirety. "This is the first time that a metabolomics platform has actually been demonstrated to solve a real-world biological problem."
He specifically pointed out that the team's nontargeted approach allowed them to identify the importance of sarcosine, which, Beecher said, was an "obscure" amino acid prior to the study, in the progression of prostate cancer.
In their paper, the scientists describe using mass spectrometry to profile more than 1,100 metabolites from tissue, blood and urine samples from men with prostate cancer. In the course of their study, Chinnaiyan said, "we identified at least ten metabolites that were elevated during prostate progression to metastasis." The team decided to focus its efforts on sarcosine because it was "consistently elevated in metastatic or aggressive prostate cancer. It was also elevated, to a lesser degree, in clinically localized prostate cancer."
Sarcosine is particularly interesting because from a biomedical standpoint, it may be useful in two ways. "Not only was sarcosine potentially a biomarker for prostate cancer aggressiveness, but it may actually be involved in the biology of cancer aggressiveness and invasiveness ... suggesting that pathways that are perturbed or that lead to sarcosine production may be novel avenues for therapeutic intervention."
In cell culture studies, the team found that sarcosine levels were higher in invasive prostate cancer cells than in benign prostate cells. Sarcosine seems to be not only a marker for the disease, but a driver of it as well: adding sarcosine to benign prostate cells caused them to become invasive. By manipulating levels of the enzymes that regulate sarcosine metabolism, the researchers found they were able to control the invasiveness of benign and malignant prostate cells.
Sarcosine is present in the urine of men with prostate cancer, raising the possibility that a urine test might one day be able to replace biopsies. Asked about this possibility, Wei said, "Right now I would say that we don't have enough confidence in these new biomarkers to do that, but it might be possible in the future."
The IP relating to sarcosine and its applications has been licensed to Metabolon by the University of Michigan. In a press release, Metabolon said it "plans to make available a research tool for investigators to better understand tumor aggressivity in prostate cancer and other cancers."
Metabolon does not engage in drug discovery or development itself, but CEO John Ryals told Medical Device Daily's sister publication, BioWorld Today, that the company is "open to and seeking partners for the development of therapeutics aimed at the sarcosine pathway."