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Thirty years ago, cancer was a black box. Researchers knew what went wrong in the body, but not how or why. The work of Robert Weinberg, professor of biology at MIT and a founding member of the Whitehead Institute for Biomedical Research, has helped researchers open that box. Weinberg discovered the first cancer-causing gene and the first tumor-suppressing gene in the early 1980s. Since then, hundreds of such genes have been discovered, and this “treasure trove,” as Weinberg calls it, has led to many new drugs. Weinberg is also helping make sense of a vast amount of complex genetic information by finding global regulators of processes common to all cancers.

Technology Review talked with Weinberg about his research into one of these basic processes. Metastasis–the spread of cancer from its initial site to other places throughout the body–is responsible for 90 percent of cancer deaths. Weinberg suggests that preventive steps, such as taking vitamins, will be key to reducing cancer deaths.

Technology Review: How does metastasis work, and how are cancer stem cells involved?

Robert Weinberg: Until recently, most people–certainly myself–believed that all the cancer cells within a tumor were essentially equivalent to each other. But over the last three or four years, there’s come increasing evidence that within solid tumors, as well as blood-born tumors, there is a hierarchy of cancer cells, with some cells being more important than others. A cancer stem cell is defined as a cell that, when plucked out of the tumor and introduced into a new host like a mouse, is able to spawn an entirely new tumor.

Cancer cells initially invade locally in the nearby tissue. Some cancer cells are able to invade into the circulation. They are then carried to distant sites within the body, [escape from circulation,] and invade into adjacent tissue. There they are able to survive and form what’s called a micro-metastasis, which represents a tiny little colony of cancer cells which more often than not fails to develop into a tumor for a variety of reasons, not all of which we understand. On rare occasion, one of those disseminated micro-metastases may indeed figure out a way of growing into a macroscopic metastasis, and as such, it may for the first time create a life-threatening growth.

TR: What is it that allows these cells to form new tumors?

RW: It’s now increasingly apparent that one mechanism, quite possibly the dominant mechanism, involves the ability by the cancer cell to resurrect early embryonic behavioral programs. [In the embryo, these programs] normally enable different tissues to form and depend on the ability of embryonic cells to move from one site in the body to another. This movement in the embryo is superficially similar to metastasis. The way cancer cells acquire this embryonic trait of being able to move throughout the organism depends on their ability to resurrect these early embryonic behavioral programs, which they do through their ability to induce the expression of early embryonic transcription factors [proteins that control the expression of a large number of genes]. In this case, these transcription factors control groups of genes that, when turned on, allow the cancer cells to move, to become invasive, to resist programmed cell death (which otherwise threatens their existence once they leave the primary tumor), and even to release degradative enzymes that break down the [surrounding tissue that] represents an impediment to the forward march of the cancer cells.

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Credit: Tan Ince (top), Sam Ogden/Whitehead Institute (bottom)

Tagged: Biomedicine, cancer, stem cells, tumor, embryo

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