Winning the War on Cancer
A growing understanding of Canada’s top cause of premature death has led to a new wave of screenings, treatments-and hope.
Prue Boyd, 65, of Nanaimo, B.C., developed a gastrointestinal stromal tumour-or GIST, as it's called-in her stomach in January 1999. Though she was a nurse, she didn't know much about this kind of cancer. As she started to learn more, she realized she was in for quite a fight. Her GIST was aggressive. The only option was surgery to remove the tumour, but the chance of that being successful was only 50 percent. Still, she had the surgery, and afterwards the physicians were optimistic-they'd got the whole tumour, they told her. But by December, the cancer was attacking her liver.
The disease had returned, and it was nearly certain it would continue to spread-and quite quickly. Despite the bleak odds, Boyd wanted to prolong her life; she went under the knife again in April 2000. At year's end, the cancer was in her abdomen. Boyd very likely had little time left.
Nevertheless, hoping for something new, her doctors sent her to the B.C. Cancer Agency in Vancouver. Boyd recounts, "I just happened to be there when they got word there was going to be a drug trial later in 2001." When asked whether she wanted to be in it, she didn't hesitate in accepting. She began taking the drug Gleevec in July 2001. "So far, it's doing its job," she says. Her tumours have shrunk and no new ones have appeared.
Eight years after her initial diagnosis, she says, "I'm alive. I feel wonderful." Now retired, she gardens, works out at the gym four times a week, travels and enjoys her two children and four grandchildren.
"Gist and Gleevec is an amazing story. It is jaw-dropping," says Dr. Calvin Law, a surgical oncologist at the University of Toronto's Sunnybrook Health Sciences Centre. "I love happy stories and this is one of them." Originally, the drug was developed to fight chronic myeloid leukemia, or CML, which is caused by a genetic mutation that stimulates cancer cells to multiply wildly. "Gleevec is like a key that locks down the mutation," explains Law. It just so happened that GIST had the same mutation, the same keyhole.
Before Gleevec was developed, 50 percent of GIST patients who could not have surgery would die within 15 months. With the drug, of the patients who can't have surgery, 50 percent live almost five years. "We often spend billions of dollars to get a two or three percent increase in survival. This is way out of the park," says Law.
In April 2007, a trial to test what happens when Gleevec is given to patients after surgery (but before the disease has had a chance to recur) was stopped. "There was such a significant decrease in disease recurrence that an independent monitoring committee felt it wasn't fair to give people a placebo. Everyone was switched over," says Law.
Michael Wosnick, executive director of the National Cancer Institute of Canada, says cancer's not a death sentence anymore. He points out that in the 1940s, in the institute's early years, only 25 percent of people newly diagnosed with cancer survived; now, 60 percent do. "We still have a lot of work to do. But cancer shouldn't be the dreaded C word," he says. Some cancers may be found to be easily cured, others might not. Still others likely will be like diabetes-chronic diseases that patients live with and manage. Like Boyd's GIST: Controlling her condition is a simple matter of taking Gleevec four times a day.
"The improved outcomes are due in part to the fact that people are starting to heed messages about healthier lifestyles," Wosnick says. "But they are also due to understanding, at a cellular and molecular level, the causes, enabling us increasingly to personalize medicine. This is far from the old 'hit the broad side of the barn' kind of approach. The more we understand what makes cancer tick, the more we can design treatments to exploit a unique feature of cancer cells."
Lisa priebe, a North Vancouver woman, had mammograms three years running-with results in the all-clear. But in May 2003, less than a year after her last mammogram, her husband discovered a lump in her left breast. About the size of a large cherry, it was malignant. Priebe, then only 42, was shocked. "My first reaction was, I have to do everything possible to ensure I'm around for a long time. My daughters were four and six. My worst fear was them growing up without a mother."
Priebe had a mastectomy, then learned the cancer had started to invade her lymphatic system. So she had six months of chemotherapy and five weeks of radiation. Then her oncologist told her about a new drug called Herceptin, which was being tested in a clinical trial and was believed to reduce the likelihood of cancer recurrence. Priebe jumped at the chance to be included in the trial. In April 2004 she started the year-long process of getting Herceptin injections every three weeks. Since then, she has been cancer free. "I feel so lucky," she says.
Herceptin is one of the most remarkable drugs in the new wave of targeted therapies. It's an antibody to a protein that about one third of all breast cancers make in abundance, explains Dr. Caroline Lohrisch, a medical oncologist at the B.C. Cancer Agency. Normally, cells contain two HER2 genes, which play a role in regulating cell growth. But for reasons no one understands, in some cancer cells there are multiple copies of the gene, which results in the production of excess amounts of HER2 protein,
resulting in abnormally accelerated cancer-cell growth. Herceptin inhibits the production of extra HER2 protein. It isn't for everyone-it only benefits people whose breast cancers create too much HER2 protein. But four studies involving a total of 10,000 subjects with this type of breast cancer have shown that 50 percent fewer patients relapse when a year-long treatment with Herceptin is part of the chemotherapy program.
Researchers are exploring whether another drug, Abraxane-an updated version of a chemotherapy drug called paclitaxel, which must be dissolved before it can be delivered to the body via the bloodstream-can be used in a targeted way. Investigators learned that when paclitaxel was suspended in albumin-a protein naturally found in the body-patients with advanced breast cancer had fewer side effects and better results. Then, scientists speculated some breast cancer cells produce extra amounts of a protein called SPARC, which binds to albumin. The theory is that Abraxane-which is attached to the albumin-will be pulled into the cancer cells by SPARC, where the drug can then kill these cells. A Canadian clinical trial is testing the idea, says Dr. Susan Dent, a medical oncologist at the Ottawa Hospital Cancer Centre. If the trial is successful, physicians would know which patients are most likely to benefit from Abraxane. Says Dent, "We are moving away from one-size-fits-all."
Cancer's Achilles Heel
Our understanding of the genetics of cancer have led to another exciting development in which Canadian researchers are playing a leading role. In order for cancer cells to grow as aggressively as they do, they had to make a "deal with the Devil," says John Bell, a senior scientist at the Ottawa Health Research Institute. He explains that for cells to multiply wildly, they have to give up some gene products; and when they do, they lose the ability to fight virus infections.
In 2005, researchers from Calgary and London, Ont., made headlines nationwide by killing malignant brain tumours in mice using a pox virus harmful only to rabbits. Ninety-two percent of the mice were alive and, apparently, cured when the experiment was over. What makes this type of therapy very appealing, says Bell, is unlike chemotherapy or radiation, the virus doesn't attack noncancerous tissue. In fact, it has been developed to exploit a genetic defect in the tumour-nontumour cells don't have this defect, so they won't be targeted.
Funded in part by the National Cancer Institute of Canada, a small clinical trial involving Hamilton, Ottawa and Calgary subjects with solid tumours will further test this cancer-fighting avenue, using the virus from smallpox vaccines, cowpox, which doesn't cause disease in humans.
Though widespread screening has led to earlier diagnosis in several types of cancer, current methods are not perfect. For instance, a commonly used blood test for prostate cancer, the PSA test, is used to detect an enzyme called "prostate specific antigen." An elevated level means a prostate problem, but it doesn't necessarily indicate cancer. Improvements upon this test may be coming: A new way to identify prostate cancer tumours-using patterns of gene expression from DNA microarray data-is being developed at the National Research Council Institute for Information Technology facility in Moncton, N.B. Nabil Belacel, a research officer with the institute, says this improvement would allow scientists to analyze the patterns of gene activity in a cell and to identify biomarkers of prostate cancer.
Breakthroughs in Diagnosis
In addition to detecting structural abnormalities in the body, scientists are now also able to look for functional problems due to advances in imaging techniques. "Tumours use glucose in a different way from normal cells-they hang on to it longer; they use more of it," explains Dr. Sandy McEwan, chair of the Department of Oncology at the University of Alberta as well as the head of imaging at the Cross Cancer Institute in Edmonton. He says observing glucose metabolism is a very good way of detecting certain kinds of cancer, such as melanoma, and lung, breast and bowel cancer. PET scans (which measure metabolism) can pick up tumours too subtle or small to be seen by CT scans (which are imaging tools alone), he notes. There's also evidence that decreases in glucose metabolism are good indicators of how well a tumour is responding to treatment. "This is still at the being-proven stage," says McEwan, "but for lymphomas, some rare sarcomas, and breast cancer, it's looking pretty convincing." A clinical trial to test the concept is about two or three years away.
MRI technology, meanwhile, is proving to be a promising addition to the imperfect art of mammography. In a breast-cancer-screening study of 500 very high-risk women, Dr. Ellen Warner-a medical oncologist at Toronto's Sunnybrook Health Sciences Centre-found MRIs detected 82 percent of new cancers, compared with 33 percent for mammography, 41 percent for ultrasound and nine percent for physical examination. The combination of all four methods detected 97 percent of the newly diagnosed cancers.
Warner does not advocate using MRIs as part of a mass screening program, however. "They have a high rate of false positives, making them unsuitable for women with an average risk of developing the disease." But for those five to ten percent of women coping with the high risk of developing hereditary breast cancer, this technology can be a real lifesaver.
Tony Redler, a 52-year-old resident of Regina, is another living testament to the power of our growing understanding of cancer. "I'm a firm believer that, without research, I'd be dead." He was diagnosed with a form of Hodgkin's disease in 1982. Treated with an aggressive chemotherapy and radiation regime, the disease went into remission until 1990, after which more chemotherapy followed. When his cancer again returned, in 1992, a bone-marrow transplant to fight the cancer was a new option. Redler was one of the first Canadians to have this transplant for his particular disease. But in 1995, the malignancy rebounded. This time, Redler had a stem-cell transplant-innovative at that point-as well as a second bone-marrow transplant. "That's when it quit," says Redler, who's been disease-free ever since.
"Life's got its tough moments, but I'm on the plus side of the grass," he says. "I've seen my grandbabies. That's all that matters."