Paul Nghiem keeps an old Kodachrome slide taped above the desk in his office. It shows a close-up of a man’s lip. Scribbled beneath the photo is a date: May 1996.
At the time, Nghiem was a young dermatology resident in Boston. This patient had come in because of a funny bump on his lip. Nghiem did a biopsy, and the results came back as a very rare, very deadly form of skin cancer: Merkel cell carcinoma (MCC).
While Nghiem had heard of MCC, it was the first case he’d ever seen. Yet that lone case was enough to qualify him as an expert—at least according to his mentor, who happened to be on the hook to write a book chapter about MCC. He asked Nghiem to lead the writing project.
What a complete waste of time, Nghiem thought. But he couldn’t say no.
Saying yes transformed his career. Merkel cell carcinoma morphed from a chore to a moderately interesting subject to a two-decade whirlwind of clinical, basic and translational research.
That constant back-and-forth between lab and clinic has led to pioneering new tests and treatments for patients with MCC, including last fall’s announcement of the first FDA-approved immunotherapy drug to treat the cancer. These advances were unthinkable in May 1996, when that first patient with MCC walked into his clinic.
He’s seen more than a thousand since. And while Nghiem loves spending long hours in the lab, unravelling the mysteries of MCC, the Kodachrome slide above his desk reminds him why all the effort is worthwhile.
“It’s an honor to take care of patients during such an important time in their lives,” said Nghiem, head of UW Dermatology and an investigator at Fred Hutch. “We work as a team to provide the best care for patients and to drive the science forward in powerful ways that are affecting the way care is provided around the world.”
A deadly foe
The deeper Nghiem dug into MCC for his textbook chapter, the more intrigued he became. It takes its name from the Merkel cells present in touch-sensitive areas of our skin like our lips and fingertips. While dermatologists don’t believe MCC is derived from normal Merkel cells, the tumor cells closely resemble them.
What was always apparent was its aggressiveness. “It’s one of the most lethal forms of skin cancer, killing upwards of a third of all patients diagnosed with it,” Nghiem said.
Around 2,000 patients are diagnosed with MCC each year. After the book chapter was published in 2001, Nghiem started to hear from some. By 2006, when he moved to Seattle, Nghiem was following 200 patients.
In 2008, researchers in Pittsburg discovered a brand new virus that caused most cases of MCC. That suggested a new way to treat the cancer; if a virus induced the tumor, the immune system could play a central role in controlling it.
Almost immediately, Nghiem started to hear from fellow researchers and clinicians interested in MCC. He began collaborating with relatively new neighbors at Fred Hutch and Seattle Cancer Care Alliance including Shailender Bhatia, Denise Galloway and David Koelle. They’re still at it today, developing immunotherapies that enlist patients’ own defenses to fight MCC.
“We put all our poker chips in the middle of the table and said we’re going to rely on the immune system to fight this,” he said.
For the past decade, Nghiem and his collaborators have searched for ways to get the immune system to recognize and destroy MCC. Their discoveries include an inexpensive blood test that can detect the recurrence of MCC faster than traditional scans; new tools to better study the immune system’s response to cancer; and the first FDA-approved immunotherapy drugs.
Those drugs, which help the exhausted immune system attack the tumor, dramatically improve long-term results compared to chemotherapy, long the gold standard treatment. But chemo only offered a 3 percent chance of benefit beyond a year. Immunotherapy offers 50 percent.
This fall, the National Cancer Guidelines for treating metastatic MCC will be rewritten; immunotherapy will be preferred over chemotherapy. It’s an exciting step forward, Nghiem said. But plenty of challenges remain. The biggest: nearly half of patients for one reason or another won’t benefit from the existing immunotherapy treatments. Nghiem and his collaborators want to find out why.
Although this odyssey started by accident for Nghiem, it’s not much of a surprise. He’s wanted to push boundaries since he was a boy. He initially dreamed of being an astronaut. Then he read a Michael Crichton novel called “The Andromeda Strain,” about a lethal virus that lands from outer space. Bye-bye, NASA. Hello biomedicine.
“In my life, this story hasn’t been fiction,” Nghiem said. “It’s not a space invader, but it is cancer. That has turned out to be much more interesting.”
