A new view of cancer  pg. 6

Research is continuing. Matrisian and colleagues around the world are developing biomarkers and optical imaging techniques to determine how effectively the inhibitors block the enzymes, and new animal models that more closely resemble the human condition.

Other researchers are tackling metastasis from the point of view of the errant tumor cell that makes it into the bloodstream. In patients with cancer, “there are (an estimated) million or so tumor cells circulating at any one time, and yet only one or two of those end up as metastases,” Pollard says. “Does that mean that (only) one in a million cells… is able to metastasize, or that there are a million cells able to metastasize but only a one-in-a-million chance of them lodging in the right place?”

One theory is that once out in the bloodstream or lymphatic system, the tumor cell tracks a “trail” of chemokines to a specific tissue that is producing the signal—essentially reversing the course that inflammatory cells took to get to the primary tumor. “Another possibility which is a bit… more outlandish,” he says, “is that tumor cells are ‘chaperoned’ by (blood) cells.” In either case, the spread of cancer may be guided by specific chemokines released by various tissues.

Pollard hopes the new imaging technology the Einstein group has developed will help solve the mysteries of metastasis. “We should be able to follow cells as they move around the body in ways that we’ve not been able to do before,” he says.

Ultimately, the control of cancer may depend on a better understanding of the complex chemical signals that guide these cells. “These are the big questions,” says DuBois. “How do these inflammatory cells potentiate tumor development at the molecular level? What is the precise role of the microenvironment, and what regulates the inflammatory cell recruitment into the neoplastic (tumor) microenvironment? We don’t have answers to that.”

With the help of techniques such as DNA microarray, scientists are identifying genes that play a role in inflammation and cancer. They’re studying what happens when the genes are “knocked out” in mouse models. One goal is to learn how to “manipulate” macrophages, for example, by altering the balance of cytokines in a way that would turn them from the tumor’s friend to a foe.

On the clinical side, researchers are trying to identify “bio-markers,” or patterns of proteins in blood samples from patients that can be correlated with types and stages of cancer, and their response to treatment. Another approach seeks to identify groups of patients with genetic differences, called polymorphisms, who would be most likely to benefit from targeted cancer therapies.

With these approaches, “you will have determined on some level what genetic pathways or patterns of protein expression are altered in the patient’s tissue,” Richmond explains. “Then you might be able to predict which regime to use for that patient by targeting the defect in that specific patient’s tumor.”

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