By Josh Fischman
Slaying Cancer's Dragons
Anita Roberts, a.k.a. Queen Christine, fends off cancer at work and at home
By Josh Fischman
Anita Roberts has been leading a fairy tale life, at least on the internet. At her website, www.anitaroberts.net, the National Cancer Institute scientist is the gracious Queen Christine, ruler of BellaDonna, a land of beauty and purity. Aided by her beau, Lord Robert of Bethany, she wages a valiant battle to defend her land against an attack by the crablords and their fierce dragon, Gastricus.
Her real life has, over the past two years, been somewhat less than the stuff of dreams and fantasies. In March 2004, Roberts, at age 62, was diagnosed with a true attack of the crablords: advanced gastric cancer. The internet tale was put together by her family to explain to her young grandchildren what Roberts was going through. "This gave them a way they could think about the disease," Roberts says. Christine must poison her own lands, as Roberts went through toxic chemotherapy, and then lost "her fair locks" as Roberts lost her hair—something "which really spooked the children."
Roberts herself has had to find new ways to think of her disease. A principal investigator in the NCI's laboratory of cell regulation and carcinogenesis, she shared the Komen Brinker Award for Scientific Distinction last December for her work on molecules that can turn a healthy cell cancerous. But she has had to reconcile being a cancer researcher interested in biochemistry with being a cancer patient interested in a cure. "When I was first diagnosed with this cancer, I was so angry about my research. I thought: ‘What have I been doing for 25 years? Who cares what compound binds to what piece of DNA?' " she says, and then pauses to laugh, shaking a full head of gray hair. "That lasted about a week. Then I realized we now have drugs based on what we understand from our basic research. Now I'm comfortable with it."
She should be. The molecules that Roberts has spent 25 years on, and indeed helped discover, are from a group of proteins called TGF—for transforming growth factor—beta. Knowledge about these growth factors has revolutionized scientific understanding of the way cancer progresses, how wounds heal, and how the two processes are related. Growth factor research has also given rise to some of the newest anti-cancer therapies, such as the breast cancer drug Herceptin (trastuzumab) and the tumor inhibitor Avastin (bevacizumab). "What she did was incredibly skillful," says Michael Sporn, Roberts' former boss at the NCI and longtime friend, who is now at Dartmouth Medical School. "She has this great combination of being smart and insightful, with real people skills. She's very good at getting people to work together. You just meet her and you know she's good to be around."
Roberts and Sporn found that TGF-beta is a "superfamily" of proteins that control the growth of epithelial cells-which line the skin, breast ducts, lungs and gastrointestinal tract—as well as lymphoid cells, which are a type of white blood cell. Together these two cell types are involved in nearly 90 percent of all human cancers. TGF-beta is linked to such cancers because of its Jekyll-and-Hyde personality. Normally the protein, starting outside the cell, sends a signal inside that tells the cell to stop growing. But if that signal is altered, the reverse happens, and the reverse is bad. Cell growth can run amok, and that means cancer. So what Roberts is trying to do is figure out how that signal can go awry. It turns out that the "no grow" signal is carried from TGF-beta into the cell by a series of other proteins called Smads, which interact in a lot of complicated ways. Changes in their signals flip this "no grow" message to one that actually promotes the spread of cancer. Roberts is now trying to untangle the Smad pathways, to figure out what happens that turns TGF-beta from a good guy into a villain.