Smarter Drugs

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.