Drivers wanted
Dana-Farber physician-scientist Lynda Chin searches for genes involved in the origin or progression of cancer.
The goals of biomarker scientists shouldn't obscure the difficulties they face. Despite all that has been learned, only a handful of discoveries have successfully made the passage from the laboratory to clinical tests for bona fide biomarkers.
The sheer complexity of cancer and the genetic variability of tumors, even among those that look similar under a pathologist's microscope, can make it difficult to predict a tumor's clinical course. Studies of genetic activity within a single type of cancer – metastatic melanoma, say – tend to turn up hundreds of points of difference from the activity in normal cells.
"These studies often provide you with a long list of possibilities that include both the 'smoke' and the 'fire,'" the cloud of potential biomarkers shrouding a much smaller group of actual ones, explains Dana-Farber's Lynda Chin, MD.
Such correlative studies are useful in the initial stages of research, providing a "first cut" of candidate markers, she adds. But because cancer is such a diverse disorder, it's necessary to distinguish between substances that are merely associated with the disease and those that are actually driving it.
Chin offers an analogy to buying car insurance: "One of the most predictive factors insurance companies use to set rates is the color of the vehicle: People who drive red cars are more likely to be young males with a risk-taking personality; thus the color red is a correlative marker for a high-risk driver. A more definitive marker would be knowing the gene or genes that dictate a high-risk personality. That is the equivalent of what we're aiming for in our biomarkers research."
In practice, that means gathering all the information possible on a particular type of tumor – not just gene-activity patterns, but also data on how it progresses in patients and how they respond to treatment, much as Fuchs and his colleagues are doing in colon cancer. It means painstakingly examining each potential biomarker gene.
"The key is functionality," Chin says." "Does the gene play a role in the origin or progression of the cancer?" Substances identified through this function-based process can actually do double duty, serving not just as biomarkers, but also – because they help the disease progress – as targets for therapy. In their research in melanoma skin cancer, for example, Chin and her colleagues are searching for genes that enable aspiring cancer cells to migrate, invade tissue, and acquire "anoikis resistance," the ability of cells to survive independently in the blood. Such genes would provide valuable biomarkers for tumors that are likely to metastasize.
