Scientists are cataloging the DNA of exceptional survivors for study,
Jan Crisitello, a 70-year-old grandmother of four, was diagnosed in 2002 with stage 4 melanoma, which kills the vast majority of its victims within five years. Although chemotherapy helped her make it past the five-year mark, by 2007 the cancer was growing again. Desperate, she joined a 29-patient trial of a drug being developed by Pfizer (PFE). The drug was a failure for almost all of the patients, and Pfizer spokeswoman Sally Beatty says it has been “deprioritized for further development.” For Crisitello, the drug worked, and her cancer is in full remission. Now oncologists are studying her DNA to determine how her genome may have made her unusually responsive to the drug. “I feel very fortunate,” she says. “It would make me feel good if they found out why and could replicate that for other people.”
So far, about 100 exceptional responders have been identified by researchers poring through roughly a decade’s worth of clinical trials, says Barbara Conley, associate director of the NCI’s cancer diagnosis program. Starting in June, she says, the institute will urge researchers and doctors nationwide to send in clinical data on these patients. “We want to cast a broad net,” Conley says. “The key is, can you find another patient with the same kind of abnormality, and will they respond?”
In a study presented in early April at the American Association for Cancer Research meeting in San Diego, researchers analyzed the case of a 57-year-old woman with advanced thyroid cancer whose tumor “melted away” during a drug trial and didn’t start growing again for 18 months, according to the study’s lead author, Dana-Farber instructor Nikhil Wagle. Although the rare, aggressive disease kills most victims within five months, an analysis of the patient’s genes showed that a mutation made her tumor responsive to Novartis’s (NVS) Afinitor, a drug typically used to treat kidney or breast cancer. Researchers plan to conduct further trials with thyroid cancer patients who have similar genetic mutations, Wagle says.
One of the first exceptional responders to have her genome sequenced has a similar mutation and saw her bladder cancer go into complete remission after she took Afinitor, says David Solit, director of the Center for Molecular Oncology at Memorial Sloan Kettering. He’s been seeking out surprising cases of cancer recovery ever since, trying to identify drugs that would be effective against diseases for which they weren’t intended. “I meet with clinical teams and often see these patients who have dramatic results to compounds not moving forward because they failed in a population,” Solit says. “These are mysteries we’ve always tried to solve, but we didn’t have the tools until now to figure out the variation of responses in patients.”
The challenge is to find a drug that even an ideal patient won’t develop a resistance to, says Lecia Sequist, an oncologist at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School. People with advanced melanoma such as Crisitello are usually prescribed ipilimumab, a drug sold by Bristol-Myers Squibb (BMY) under the name Yervoy, but only 1 in 5 patients benefits from it, says Crisitello’s doctor, Lynn Schuchter. “While we’ve made huge advances in immunotherapy in recent years,” says Schuchter, the chief of hematology-oncology at the University of Pennsylvania’s Perelman School of Medicine, “we are still in the dark ages as to who should get the drug and why they are benefiting.”
Via Dr. Stefan Gruenwald