In the neighborhood
Scientists probe the impact of tumors' 'microenvironment'
By Robert Levy
In the bone marrow, multiple myeloma cells (blue) take advantage of their surroundings by attaching to marrow cells (green and white), feeding off of blood vessels (top right), and causing activated marrow cells (red) to release growth-stimulating
substances (yellow).
Illustration by John DiGianni
The notion that cancer research could stop at the cancer cell's edge didn't last very long.
From virtually the beginning of modern medical research in the late 19th century, scientists have found compound after compound able to kill colonies of cancer cells in laboratory glassware. When such compounds are tested in living systems — laboratory animals or patients — however, their cancer-killing powers often seem to vanish.
Why? One reason has little to do with cancer cells themselves, but with the cells and tissue around them, their "microenvironment." Cancer's origins, growth, spread, and vulnerability to treatment are uniquely dependent on the relationship between tumor cells and their noncancerous neighbors. This knowledge is already taking practical shape in novel therapies that interfere with the tumor-microenvironment "dialogue," the exchange of signals between malignant and normal cells, thereby making the microenvironment less hospitable to cancer's presence.
"By focusing on the microenvironment and how it interacts with cancer cells, we're finding new ways to target tumor cells and evict them from the molecular 'neighborhood' that they need to survive," says Ken Anderson, MD, chief of the Division of Hematologic Neoplasia at Dana-Farber and the Kraft Family Professor of Medicine at Harvard Medical School. "As we come to understand these interactions more fully, we're developing treatments able to overcome the traditional problem of drug resistance," in which tumors gain the ability to withstand treatments that are initially effective against them.
"In many ways, multiple myeloma offers a framework for studying the microenvironment's influence in all kinds of cancers."
—Ken Anderson, MD
Although scientists have long been aware that the microenvironment is not an innocent bystander in cancer, the vast majority of existing therapies are directed against tumor cells themselves. The reason: Until recently, scientists haven't had the tools to explore the connections between tumors and their environs in molecular detail. Now that such tools exist — in laboratory techniques and technology for scanning the genetic activity of cancer and normal cells, for penetrating the web of chemical signals between cells, for mobilizing the immune system as a tumor fighter – research into the microenvironment is winning new scientific disciples.
The disease in which such research is most advanced, and has had the biggest impact, is multiple myeloma — a relatively rare, and sofar incurable, cancer of the bone marrow. Dana-Farber investigators have tapped into key portions of the molecular "conversation" between myeloma cells and their surroundings. Already, their efforts and those of researchers at other institutions have resulted in federal approval of three medications that are brightening the prospects for thousands of myeloma patients.
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