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Some 1.75 million new cases of cancer will be diagnosed in the U.S. this year, the National Cancer Institute estimates, and more than 600,000 people will die. But St. Louisans facing cancer often have a fighting chance nowadays, thanks to cutting-edge research and treatment pioneered at local institutions and hospitals.
New insights into cancer’s genetic makeup lie behind many of these advances. Washington University was one of three genome sequencing centers nationwide, working in concert with genome analysis centers, that recently completed The Cancer Genome Atlas, funded by the National Cancer Institute. The project identified 300 genes that drive tumor growth in 33 major types of cancer. Those findings are enabling cancer researchers to develop more effective treatments and ushering in a new era of personalized medicine, or precision medicine, says Dr. Jonathan Heusel, chief medical officer at Wash. U.’s Genomic and Pathology Services.
“It’s a very, very diverse field,” says Dr. Heusel, “that is actually changing all of medicine, because this technology reveals information that is useful not only for cancer but also any type of inherited or developmental condition. When physicians have that kind of information, they can begin to target therapies specific for the patient as opposed to treating them based on large clinical trials for a particular disease.”
For example, Dr. John DiPersio and his research team at Siteman Cancer Center at Barnes-Jewish Hospital have employed a gene-editing tactic to treat certain blood cancers with the use of immunotherapy. In cancer patients, the T cells that typically fight off the disease have lost the ability to do so. DiPersio’s team successfully extracted such cells from patients and, using CRISPR gene-editing technology, modified them to home in on and destroy cancer cells, then reintroduced them into the patient.
“These are living cells that expand dramatically in the patient’s body and kill the target tumors,” says DiPersio, adding that they’re “phenomenally effective” with certain cancers. Clinical trials conducted in children with acute lymphoblastic leukemia and adults with lymphomas and multiple myeloma—patients whose disease had not responded to treatment or had relapsed—had remission rates of 40–80 percent. In comparing that to a zero chance of recovery, DiPersio says, “That’s quite a difference.”
Examining Side Effects
The good news: More Americans—some 16 million—are survivors of cancer. The bad news: Many suffer long-term side effects of certain forms of treatments.
A common side effect known as chemotherapy-induced neuropathic pain—often manifesting as debilitating numbness in hands or feet or pain in limbs—can linger for years and deter patients from seeking cancer treatment.
“In the majority of patients, once the pain develops it never goes away,” says Saint Louis University pain specialist Daniela Salvemini, professor of pharmacology and physiology. “Millions of individuals are cancer-free but left with this major issue that has a major impact on their quality of life.”
Until now, there have been no proven strategies for CINP prevention or treatment, but Salvemini may have found an answer. In animal studies of the common chemotherapy drug oxaliplatin, her team identified and developed a molecule that “can not only block the development of the pain but also reverse it after the pain develops without interfering with the anti-cancer action,” she says.
Salvemini hopes to begin human clinical studies in the next couple of years, enrolling patients before chemo and patients who already have CINP, “so we have both preventive and treatment paradigms.”
Similarly, cardio-oncologist Dr. Daniel Lenihan, who directs the Cardio-Oncology Center of Excellence at the Washington University School of Medicine, concerns himself with the impact of cancer treatment on patients’ hearts. The center is among the first in the country to develop cancer treatment plans intended to mitigate or prevent unintended negative effects on the heart.
“We’ve learned this lesson many times over that those targets for cancer have common biologic process in the cardiovascular tissue,” Lenihan says. For example, he noted cardiac injury in breast cancer patients undergoing HER2-targeted therapy. “We went and looked at the heart muscle cells,” he says. “Lo and behold, there’s a HER2 receptor on a heart muscle cell. We had no idea to even look for that in years past.”
That’s because patients and doctors were just trying to beat back cancer rather than also focusing on cardiac ramifications years down the road. Now that many cancer patients are living longer, however, Lenihan and his colleagues are trying to both prevent and treat such manifestations. “For the people who are long-term cancer survivors, we’re sort of reacting to events that happened a long time ago,” he says. “What would be much better is to react to things right now and prevent them.”
To do that, he and his group remain vigilant, working to identify how therapies, including next-generation immunotherapies, are affecting the heart. “We certainly want to care for the patients in front of us—the ones who are being treated right now—to try to have the best available strategy to keep them as healthy as possible, but I also don’t want forget about the patients who already got treatment. They need to know that many of the treatments that they got in the past, although they were great for the cancer, have other manifestations. We need to stay on top of that.”
