The oncologist was blunt: Stefanie Joho’s colon cancer was raging out of control and there was nothing more she could do. Flanked by her parents and sister, the 23-year-old felt something wet on her shoulder. She looked up to see her father weeping.
“I felt dead inside, utterly demoralized, ready to be done,” Joho remembers.
But her younger sister couldn’t accept that. When the family got back to Joho’s apartment in New York’s Flatiron district, Jess opened her laptop and began searching for clinical trials, using medical words she’d heard but not fully understood. An hour later, she came into her sister’s room and showed her what she’d found. “I’m not letting you give up,” she told Stefanie. “This is not the end.”
That search led to a contact at Johns Hopkins University, and a few days later, Joho got a call from a geneticist co-leading a study there. “Get down here as fast as you can!” Luis Diaz said. “We are having tremendous success with patients like you.”
What followed is an illuminating tale of how one woman’s intersection with experimental research helped open a new frontier in cancer treatment — with approval of a drug that, for the first time, targets a genetic feature in a tumor rather than the disease’s location in the body.
The breakthrough, made official recently by the Food and Drug Administration, immediately could benefit some patients with certain kinds of advanced cancer that aren’t responding to chemotherapy. Each should be tested for that genetic signature, scientists stress.
“These are people facing death sentences,” said Hopkins geneticist Bert Vogelstein. “This treatment might keep some of them in remission for a long time.”
No sign of disease
In August 2014, Joho stumbled into Hopkins for her first infusion of the immunotherapy drug Keytruda. She was in agony from a malignant mass in her midsection, and even with the copious amounts of OxyContin she was swallowing, she needed a new fentanyl patch on her arm every 48 hours. Yet within just days, the excruciating back pain had eased. Then an unfamiliar sensation — hunger — returned. She burst into tears when she realized what it was.
As months went by, her tumor shrank and ultimately disappeared. She stopped treatment this past August, free from all signs of disease.
The small trial in Baltimore was pivotal, and not only for the young marketing professional. It showed that immunotherapy could attack colon and other cancers thought to be unstoppable. The key was their tumors’ genetic defect, known as mismatch repair (MMR) deficiency — akin to a missing spell-check on their DNA. As the DNA copies itself, the abnormality prevents any errors from being fixed. In the cancer cells, that means huge numbers of mutations that are good targets for immunotherapy.
The treatment approach isn’t a panacea, however. The glitch under scrutiny — which can arise spontaneously or be inherited — is found in just 4 percent of cancers overall. But bore in on a few specific types, and the scenario changes dramatically. The problem occurs in up to 20 percent of colon cancers and about 40 percent of endometrial malignancies — cancer in the lining of the uterus.
In the United States, researchers estimate that initially about 15,000 people with this defect may be helped by this immunotherapy. That number is likely to rise sharply as doctors begin using it earlier on eligible patients.
Joho was among the first.
Even before Joho got sick, cancer had cast a long shadow on her family. Her mother has Lynch syndrome, a hereditary disorder that sharply raises the risk of certain cancers, and since 2003, Priscilla Joho has suffered colon cancer, uterine cancer and squamous cell carcinoma of the skin.
Stefanie’s older sister, Vanessa,…