CHARACTERIZING CANCER

July 28, 1999
		Researchers recently found how normal cells turn cancerous. A study, published in the journal Nature this week, said the knowledge could lead to breakthroughs in cancer treatment and prevention. One of the authors of the study, Dr. Robert A. Weinberg, explains the findings. The Health Unit is a partnership with the Henry J. Kaiser Family Foundation.

May 19, 1999: Bone marrow transplants Feb. 18, 1999: Preventative Mastectomies Am I at risk? Sept. 25, 1998: The Cancer March May 27, 1998: Sorting out cancer research April 13, 1998: New drugs to treat breast cancer March 18, 1998: Is Vitamin E a cancer fighter? March 12, 1998: Some cancers are declining. May 30, 1996: Lawsuits against breast implant manufacturers. Nov. 25, 1996: More news about Prostate Cancer More NewsHour Health and Science coverage.	TERENCE SMITH: That research is being described as a breakthrough in understanding how normal human cells become cancerous. Scientists report in the new edition of the journal Nature that after 15 years, they have successfully created a human tumor cell. Researchers took a normal human cell, added genetic flaws, and created a cancerous cell. To explain how and why that's important we're joined by one of the study's authors and head of the lab that did the work, Robert Weinberg. He is with the Whitehead Institute at the Massachusetts Institute of Technology. Professor Weinberg, welcome. ROBERT WEINBERG: Thank you for having me.
	A normal cell to becomes a tumor cell
	TERENCE SMITH: Tell us, if you will, in layman's terms, what your team discovered. ROBERT WEINBERG: We were interested in how cancer begins, and if one looks at human tumor, one realizes it's a conglomerate of many cells which are growing, multiplying out of control. That focuses our attention on those individual cancer cells and why they're doubling at times when, by all rights, they should be silent and shouldn't be multiplying at all. If you look inside the cells, you'll see that they have a number of damaged genes. And these damaged genes are telling the cells to grow when they shouldn't be growing. These damaged genes or mutated genes, are sometimes called uncle genes or tumor suppresser genes. They're the regulators that orchestrate the proliferation of the cell. For many years, we've been trying to figure out how these damaged genes force a normal cell to become a tumor cell. The problem, however, is that if one looks at human tumor cells, as isolated from patients, these cells have an unknown number of damaged genes, and so we've been hard-pressed to enumerate all of the genetic damage that is required to convert a normal human cell into a cancer cell, into a tumor cell. But now in recent years, we've learned the identities of some of the critical genes and finally, we've been able to transform a normal cell into a cancer cell, shedding light on how cancer originates within the body. TERENCE SMITH: Why is that important to learn? ROBERT WEINBERG: Because if we want to cure cancer one day, we need to know how it begins. Without knowing the details of the damage inside the cell, we'll never be able to develop cures that are totally effective. If you don't understand a disease, you can't really cure it effectively. TERENCE SMITH: Now, there are some 110 different kinds of cancer. Which tumors were you working with? ROBERT WEINBERG: We happened to be working with connective tissue cells and cells from the kidney. But we believe that what we learned about these two kinds or cells should be applicable to a variety of cells throughout the body. TERENCE SMITH: You mentioned yourself that scientists have been working on this for years. What made it suddenly possible to break through and get this new information? ROBERT WEINBERG: The really important breakthrough in this area was a discovery several years ago of a gene called telomerase. That represents a critical ingredient in this cocktail of genes which must be altered within a cell in order for it to become transformed from fully normal to becoming a cancer cell. Without that gene in the cocktail, it would not have succeeded.
	Damaged genes inside a cell
	TERENCE SMITH: What -- I suppose the most fundamental question here is what makes a tumor grow? ROBERT WEINBERG: What makes a tumor grow is this suite of damaged genes inside a cell, which tell the cell to grow unrelentingly, in contrast to what happens in a normal cell, where the normal genes tell the cell to remain silent and not to multiply. TERENCE SMITH: You mention that this has to do with the origins of cancer, rather than specifically therapy for it. But might the information help lead to therapy for it? ROBERT WEINBERG: No doubt it will, over the next decade. Not right away, but over the next decade, because now we can begin to construct a variety of different cancer cells, each with a different group of damaged genes in it, and begin to understand how these damaged genes allow the cancer cell to respond to certain kinds of therapy, or to be resistant. Right now, we really don't understand the rules that determine whether or not a tumor will be responsive to a specific kind of therapy. In the future, we can begin to lay out a specific set of rules, which tells us in advance, in a predictive way, whether cells will respond or will not respond to the kind of therapy we'd like to apply to the tumor. TERENCE SMITH: So instead of using a sort of double-barreled shotgun approach like chemotherapy, you would do something much more targeted. ROBERT WEINBERG: Exactly, precisely. Right now chemotherapy is a bit of witchcraft, in the sense that we don't always know how it works, why it works, and if it does work, exactly what the biochemical basis of that success was. In the future, we hope to convert the whole issue of therapy more into a science, rather than what it is right now, which is bit of an art. TERENCE SMITH: In theory, I suppose this could open up other avenues of research. It could be replicated with other cancers, et cetera. ROBERT WEINBERG: Well, in fact, one should be able to make a wide variety of different cancers, and these kinds of cells should learn us -- should allow to us learn about a new area of cancer research that we don't know much about yet, and that is how cancer cells, which start at one point in the body, how they begin to spread elsewhere: The process of metastasis. Right now we don't really understand very clearly how cancers spread, and these cell which don't get spread, the ones we've made, can be used as very useful reagents with which to develop information on the process of metastasis. TERENCE SMITH: So in very simple terms, once again, if you know how and are able to actually create a cancerous cell, in theory, you can walk back the process in order to learn more about it? ROBERT WEINBERG: Exactly. We hope to be able to list with great precision the molecular defects inside a cell, which enable it to become a cancer cell, which enable it to grow as a malignant cell. So that one day, maybe a decade from now, we'll be able to look at a cancer cell and say these are the precise biochemical and molecular defects which cause it to grow abnormally. Until now, that's been an unreachable goal.
	"It's a step forward."
	TERENCE SMITH: You know, we have all witnessed and heard for years about the war on cancer. Put this in that context for me. Is it a battlefield victory? Is that what you'd call it? ROBERT WEINBERG: Well, it's a step forward. There's still many steps ahead of us. But the fact of the matter is there have been dramatic advances over the last 20 years. It's not as if we know a little bit more than we knew 20 years ago, we know an enormous amount more than we did 20 years ago. Indeed, in the mid-1970's, we really had no clear idea about how cancer begins, and now we have a very clear view of it, in many of its details. TERENCE SMITH: This must be quite a moment for you and for your team, having worked on it so long. ROBERT WEINBERG: Well, in fact, this work is the culmination of work from many different laboratories -- the synthesis of research from dozens, indeed hundreds of laboratories across the world, which fed in different ways into this work. It's a step forward, and I believe that it will lead to yet other steps the future. TERENCE SMITH: Did you find yourselves excited by this notion when you came upon it and when you were able to fully categorize it? ROBERT WEINBERG: Yes, we did, because it was satisfying to be able to do something that we had failed for so long to do-- that is to create a cancer cell out of a normal human cell, something which seemed impossible for so many years. TERENCE SMITH: So a step forward, but many more steps to go. ROBERT WEINBERG: Indeed. TERENCE SMITH: All right. Thank very much, Professor Weinberg. ROBERT WEINBERG: Thank you for having me.