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Another Whitehead scientist, oncologist Dr. Todd Golub, is trying to improve on the primitive techniques doctors use to guide their fight against cancer. Currently, pathologists use the location of a tumor in the patient's body and its appearance under a microscope to determine what sort of malignancy is involved. It works often--but not always. Melanoma, for example, starts out as a skin cancer but may end up in the lung or breast, where it can be much more damaging than primary lung or breast cancer.
Proof at the genetic level that origin means more than location is coming in. Researchers at Stanford have been studying liver, breast, prostate and lung cancers for clues to their telltale molecular fingerprints. Using microarrays to sense which genes are turned on in sample tissues, says geneticist Charles Perou, the Stanford team has discovered that most of the genes expressed by both normal breast cells and primary-breast-cancer cells are similar, and so are cells for normal lung tissue and lung cancer, normal prostate and prostate cancer, and so on--which should ultimately give doctors biochemical identifiers to guide their treatments.
Golub and colleagues at Boston's Dana-Farber/Harvard Cancer Center, meanwhile, are learning that tumors from a specific category--lung, prostate, colon--can be divided into previously unsuspected subcategories. Golub says of his specialty, for example, "We're trying to understand why some men die with prostate cancer rather than of prostate cancer, whereas others have aggressive disease that kills them."
Researchers led by Louis Staudt, an oncologist at the National Cancer Institute, have been asking similar questions about lymphoma. In a paper published in the scientific journal Nature, they showed how lymphomas that look the same under the pathologist's microscope aren't necessarily identical. Staudt and his colleagues used DNA chips to see which genetic switches were being thrown in each of 40 different biopsy samples from lymphoma patients. By looking at specific genes involved in cell proliferation and immune-cell response, says Staudt, they determined that "two different kinds of tumors are hiding within the single diagnosis of diffuse large-cell lymphoma." That, he believes, may be why only 40% of patients respond to currently available treatments: the rest are getting the wrong kind of therapy.
These sorts of tightly focused studies are already beginning to make cancer treatment more effective. Last year physicians approached the Maryland biotech company Gene Logic for guidance. They had a patient with esophageal cancer--an especially lethal type--so they wanted to find the best therapy in a hurry. Would radiation be appropriate? What about chemotherapy? And if so, which type? Or perhaps it made sense to go right to one of the new experimental antiangiogenesis medications that cut off a tumor's blood supply.
They went to Gene Logic because the company is one of a handful, along with California's Affymetrix and Incyte, that have developed DNA-chip and microarray technology--in this case, chips that can monitor some 42,000 genes in one shot--and software to analyze the results. Using these powerful tools, Gene Logic scientists tested the patient's cells alongside others from both healthy and sick people. In a few days, they completed the analysis.