arsha Moses, PhD, a researcher in Children's Hospital Boston's Vascular Biology Program, wasn't seeking publicity when the front page Boston Globe story broke, proclaiming "Hope seen for early test to detect breast cancer." Nor was she expecting the urine samples that arrived in her lab, the inquiries from physicians or the phone calls from around the world asking whether the test is commercially available.
Moses had just published a study with postdoctoral fellow Roopali Roy, PhD, showing that an enzyme called ADAM 12, when found in urine, is a reliable indicator of the presence of breast cancer. When Moses, Roy and their colleagues tested 71 urine samples from breast cancer patients, 67 were positive for ADAM 12. In contrast, only seven of 46 samples from healthy controls tested positive for the enzyme, and only at very low levels. Urinary ADAM 12 levels were lowest in women with precancerous lesions and highest in women with cancers that had metastasized (spread to other areas of the body).
ADAM 12 has no relation to the TV series of the 1960s and 70s. And testing is not commercially available, although Children's is talking to a number of companies interested in licensing it. Moses is cautious about raising expectations, but she believes that so-called biomarkers, like ADAM 12, could help usher in a new era in which cancers are detected and treated before they can even be seen by radiologistsÔø‡—and before they become a serious threat. When an early cancer is found, biomarkers could then be used to select a therapy and monitor whether it's working.
ADAM 12 is closely related to a larger family of enzymes known as the matrix metalloproteinases, or MMPs. Without these important proteins, a tumor can't expand or metastasize. In 1990, as a postdoctoral fellow, Moses published the first evidence that MMPs are needed for tumor angiogenesisÔø‡—the growth of blood vessels to nourish the tumor. MMPs, as well as ADAM 12, break down the extracellular matrix, the dense supportive structure that surrounds cells, clearing a path for new blood vessels to sprout and penetrate the growing tumor. Breaking down the matrix also enables cancer cells to chew their way out of a tumor and metastasize to distant sites in the body.
Just as clinicians routinely order tests for glucose and cholesterol, Moses envisions patients being screened for cancer during their annual checkups with a simple urine dipstick test. If biomarkers like ADAM 12 are detected, it could mean that angiogenesis has been "turned on," and that a dormant, harmless tumor is about to begin growing and spreading. If future research bears out, it might even be possible to suppress a cancer by inhibiting ADAM 12 and other MMPs. In this way, cancer could become a chronic, treatable disease, like diabetes.
"People are living long, healthy lives with diabetes because they monitor their glucose levels," Moses says. "Here's my fantasy: a doctor saying to a patient, Ôø‡eYou've got things in your urine that suggest you may have some cancer activity; we'd better check it out further.' Patients could be going home from their visits with a dipstick test and some angiogenesis inhibitors."
The report appears in the September 20 online edition of the Journal of Biological Chemistry and in the December 3 print edition.