A doyen steps down

In the beginning of Audrey Evans's career spent researching neuroblastoma, the most common cancer in babies, almost every child diagnosed with the disease would die. By the time she retired last winter after 60 years, however, that had all changed.

Early in her career in Boston, Evans recalls a pleasant surprise she received from a child who had been sent home to die. "Six months later the mother called back to say, 'would you like to follow up?' And everybody gulped." This child's cancer had regressed spontaneously. Evans and her colleagues began to realize that a significant number of kids experienced the same pleasant surprise, a finding that has helped revolutionize the scientific understanding of the disease.

At three o'clock on a Sunday afternoon last winter, after having packed up her office at the Children's Hospital of Philadelphia (CHoP), Evans quietly snuck out the back door, "with practically nobody knowing," she says with a giggle. At 84, having spent nearly half her life studying children's cancer at CHoP, Evans decided to retire. But despite her attempts to sneak away unnoticed, Evans's fingerprints are left all over the field.

Neuroblastoma tumors often form on nerves in the spinal cord and on the adrenal glands. Evans called spontaneously regressing cancers "4S," for special metastatic. By identifying 4S patients, children could avoid aggressive surgeries and chemotherapies and let the cancer evaporate. "It was a great advance to watch neuroblastoma disease disappear by itself," Evans says.

Evans and her colleagues dug down into the cancer to find out what might be involved in different types of neuroblastoma. They surfaced with the proto-oncogene TRK. Three genes in this family of receptors each correspond to a different neuroblastoma prognosis: good (stages 1, 2, and 4S), intermediate, and aggressive. Evans left much of this molecular work to her colleagues, but she opened the door to make that happen, says John Maris, CHoP's chief of oncology.

"Dr. Evans, in every respect, is the grandmother of pediatric oncology," Maris says. In addition to forming the "Evans" staging system, she did the early tests of chemotherapy treatments for children with neuroblastoma, leading to "meteoric" advances in patient survival. Maris points out that now, largely because of Evans, about 75% of children with the disease live. As the inaugural chief of the oncology division at CHoP—now a heavyweight in neuroblastoma research—Evans recruited scientists like Maris and Garrett Brodeur to lead the bench work. In turn, they followed TRK downstream to the pathways influencing the disease (Cancer Res, 62:6462–66, 2002). In 2005, the team fingered epidermal growth factor, and its activation of PI3 kinase and AKT pathways, as a culprit in the cancer's proliferation (Cancer Research, 65:9868–75, 2005). Just last year, they even found the genes responsible for neuroblastoma (Nature, 455: 930–35, 2008).

Evans also galvanized the field by starting the first meetings specifically about the disease, says Carol Thiele-Galetto, head of the cell and molecular biology section at the National Cancer Institute's Center for Cancer Research. In the 1970s, about 40 researchers gathered in Philadelphia to share findings and take notes. The most recent neuroblastoma meeting had about 400 attendants. "It's expanded to become much more international," Thiele-Galetto says. "She's been the leader of that."

Thiele-Galetto adds that Evans made sure patients with neuroblastoma were treated according to protocols based on the different stages of their disease, so any data collected from each patient included their disease stage—and that has made research all the more easy to conduct. "To get numbers to say anything for...scientific analysis, we had to take good clinical records."

Outside of research, Evans is perhaps best known for putting an end to parents sleeping in hospital hallways—she started the first Ronald McDonald House, where families of patients can stay while their child or sibling is in the hospital. That was in 1974. Now there are nearly 300 houses worldwide.

In recent years, Evans turned away from her clinical work to focus on mouse studies and testing compounds for potential neuroblastoma therapeutics. (One compound that interferes with TRK receptors is currently in clinical trials.) Evans admits she feels a little lost without her rigorous work schedule. But her colleagues are not letting her sneak away that easily—Evans's portrait will be the first of a woman to hang in CHoP's Stokes Auditorium.

Excellent article featuring Dr. Evans and her extraordinary career as a clinical researcher. Dr. Evans must be commended for helping place neuroblastoma along with retinoblastoma and nephroblastoma in the category of pediatric malignancies with well-described molecular pathophysiologies.

As an aside, the title of the piece should be "A DOYENNE steps down", as doyen is defined as "...a man who is the eldest or senior member of a group..." (from Old French doien, from Late Latin decānus, chief of ten). The feminine form of doyen is DOYENNE.