Breakthrough Medicine 02
“Probably the most potent cancer treatment known to man is to put good immune cells into your body so they can hunt down and kill your tumor cells,” says Patrick J. Stiff, the director of the Cardinal Bernardin Cancer Center at Loyola University Medical Center, in Maywood. So, a decade ago, Stiff—who focuses on such cancers as leukemia, which originates in the bone marrow, and lymphoma, which originates in the lymphatic system—pioneered a method of harvesting a patient’s own stem cells, multiplying them, and introducing them back into the body. Now he has taken that procedure another step further, using the multiplication process on donor stem cells, which, when put into a patient’s body, generate a new immune system that then takes on the cancer.
As might be expected, a cancer-stricken patient’s stem cells are often too badly damaged to be effective—which is why Stiff turned his attention to stem cells culled from donated umbilical cords. Here he confronted another problem. “You need a lot of [stem cells],” Stiff says, “a lot more than are in a sample of cord blood.” (Stiff works only with stem cells culled from his patients, adult donors, and umbilical cords; federal law prohibits the development of embryonic stem cells, which necessitates the destruction of embryos.)
Stiff says that he wants “to do something like the biblical story of the loaves and the fishes: to increase by many times this resource that is so badly needed.” Unfortunately, when prodded to multiply, stem cells generated from cord blood don’t yet bring with them all the necessary components of bone marrow.
Stiff has enjoyed some recent successes. Unlike researchers at other labs, who lose about 40 percent of the stem cells when processing cord blood, Stiff has cut his losses to just 3 percent. And he and other doctors have doubled the number of people who can receive stem-cell transplants for their cancers. If his current project works out, he says, “we can get those numbers much higher.”
Zapping a cancerous tumor with radiation is sometimes like shooting at a moving target while blindfolded. “We know that tumors move between treatments,” says Vasudha Lingareddy, the director of radiation oncology at Edward Hospital in Naperville. “Traditionally we have allowed ourselves a margin around the tumor to account for it”—which meant that radiation would also destroy healthy tissue.
Last spring, to target tumors more precisely, Edward became the first hospital in the Chicago area to use Trilogy Radiation Therapy, an image-guided treatment manufactured by Varian Medical Systems of Palo Alto, California. “It’s phenomenal,” Lingareddy says. “For the first time, you can actually see exactly where the tumor is.” Since then, the U. of C. Hospitals have also introduced the Trilogy system, which is especially useful in targeting lung and prostate cancers. To treat cancers of the brain and the spine, Northwestern Memorial Hospital and Advocate Christ Medical Center (in Oak Lawn) employ the image-guided Tomo-Therapy or Cyber-Knife system.
Further improvements are on the horizon: within the next year, Edward expects to introduce dynamic adaptive radiation therapy, which, Lingareddy says, will help doctors scale down radiation during a session as tumors shrink.
Breast and Ovarian Cancer
With help from a comprehensive study of the genetic makeup of cancers, Wendy Rubinstein, a medical geneticist at Evanston Northwestern Healthcare, has developed an inexpensive test of breast tissue to ascertain which women have a hereditary tendency toward breast and ovarian cancer. Though comparable tests are already available, they cost $3,000 a patient, says Rubinstein—eight to ten times the estimated price of her genetic array test. Once administered, that test can be the first step in helping women whose relatives had breast or ovarian cancer determine whether they need to take additional measures—such as a mastectomy or ovariectomy—to prevent getting the cancer themselves. “If you carry one of these gene mutations, your risk of getting breast cancer is about 80 percent, and your risk of ovarian cancer is 40 percent,” Rubinstein says. “You don’t want to allow this trait to hide in your family tree.”
Down the line, Rubinstein expects the test will also be used to tell whether women already diagnosed with breast cancer have these hereditary mutations. Based on the test results, doctors should then be able to make timely decisions about the proper course of chemotherapy treatment to recommend for a patient.
Calibrating a patient’s chemotherapy also figures into Melody Cobleigh’s research. Using data from the Human Genome Project and other related studies, Cobleigh—the director of the Comprehensive Breast Cancer Center at Rush University Medical Center—can determine which women with specific types of cancerous breast tumors are at the greatest risk of developing another breast cancer in the future. Armed with this knowledge, she can tell which patients will benefit from an aggressive regimen of chemotherapy, while also preventing patients at low or no risk of recurrence from undergoing that ordeal.
“We had been telling pretty much all patients with tumors bigger than a centimeter that they needed chemo, because we couldn’t tell who needed it and who didn’t,” Cobleigh says. “But [chemotherapy] benefits only about 4 percent of the people who get it. Now we have this predictive test that can tell some women they don’t need chemo."
After developing an experimental drug they hoped would help treat colon cancer, California’s Onyx Pharmaceuticals and the German giant Bayer brought it to the University of Chicago Hospitals for a test run. After several years of testing, Mark Ratain, the associate director for clinical sciences at the hospitals’ cancer research center, reported that trials of the drug—now called Nexavar—showed that it not only countered colon cancer, but also helped prevent the growth of kidney cancers as well.
Ratain’s trials demonstrated that, while there was no significant shrinkage of cancerous tumors—contrary to expectations—the drug did slow tumor growth. “That’s what we pride ourselves on: taking on these promising drugs and figuring out what they can do,” Ratain says. “The drug companies create the hardware, and we write the software.”
Nexavar is one of 286 drugs undergoing trial at the U. of C., says Michelle LeBeau, director of the hospitals’ cancer center. Lately, she says, cancer research has created increasingly specific, almost custom-tailored drug regimens. One vivid example of what she calls “personalization of care” is the test that Ratain helped develop to predict the toxicity of Camptosar, a Pfizer drug for colorectal cancer that has also proved effective in treating lung and breast cancers. Ratain discovered that in some Camptosar users, their white blood cell counts plummeted, which increased their risk of infection. With those findings in hand, a medical company recently developed a genetic test that oncologists can use to determine if their patients have the chromosomal makeup that might rule out Camptosar.
Another drug undergoing trials in Hyde Park is methylnaltrexone, a “peripheral opiate antagonist” that eliminates constipation, nausea, and other unpleasant side effects from morphine. The drug entered into the Food and Drug Administration’s approval process this past fall.