Biomarker discovery bodes well for better cancer diagnostics

While new findings from Ohio State University scientists suggest a genetic marker that could help distinguish between chronic pancreatitis and pancreatic cancer and gauge who will do well with cancer treatment, a pharmacologist at the Kimmel Cancer Center at Jefferson in Philadelphia sees the discovery as much more.

The researchers have identified "a new level of biological regulation" and potentially an improved way to profile tumors, says Scott Waldman, M.D., Ph.D., professor and chair of pharmacology and experimental therapeutics at Jefferson Medical College of Thomas Jefferson University in Philadelphia, who co-wrote an editorial about the study appearing May 2, 2007 in the journal JAMA, the Journal of the American Medical Association.

"The findings are significant because they seem to represent a large part of the machinery in the cell that regulates the processing of information from chromosome and gene to the protein machinery that makes the cell run," says Dr. Waldman. "No one knew about this intermediate level of regulation in every cell in the body. It's part of the cell's normal machinery that regulates in part how cells become specialized."

The Ohio State team found that preliminary evidence suggesting that the expression pattern of microRNA (miRNAs) , small pieces of noncoding genetic material , may be useful in distinguishing between chronic pancreatitis and pancreatic cancer and may be able to tell which pancreatic cancer patients will live longer than others. In humans, aberrant expression of miRNAs contributes to cancer by either turning on cancer-causing genes or by inhibiting tumor-blocking genes.

As a result, Dr. Waldman notes, the findings also indicate that these miRNAs can serve as diagnostic markers. "Because they are involved in processes underlying cancer, these specific miRNAs mediate the disease process in different types of cells, such as pancreas or lung, for example," he says. "There apparently is a profile of miRNAs that identify pancreatic cancer cells from other types. It appears that in some cases, there are common miRNAs, and for others there are miRNAs that can distinguish different types of cancer. A tumor can be profiled based on miRNAs."

MiRNAs cans serve as prognostic markers as well. "They apparently distinguish normal pancreas tissue from inflamed tissue from cancer, and this paper shows miRNAs correlate with who will do well and who won't," Dr. Waldman explains. "Presumably, it follows that miRNAs could be predictive markers, which could have implications for therapy.

"On top of this, there is a new layer of biology that is identifying novel mechanisms involved in the causation and progression of cancer, and which identifies new potential molecular targets that we can direct therapeutics against."

Yet, he cautions, "There is a great distance between biomarker discovery and application in the doctor's office." Validating such biomarkers require "well designed, prospective, multicenter clinical trials that need to show not only what the biomarkers are supposed to show, but also that they affect patient outcome."