A patient's dramatic treatment success points to ways to help others with stomach and esophageal cancers.

Joseph McGlone, a patient at the Massachusetts General Hospital Cancer Center, is one of the fortunate few whose aggressive form of gastroesophageal cancer was beaten back by an experimental drug. Within four months after his oncologist Eunice Kwak, MD, PhD, started him on a drug that targets one of his cancer’s genetic mutations, the disease completely disappeared. It has not reappeared in almost five years since.

It’s as if the drug were custom-made for his tumor. And that is teaching his team of physician/researchers lessons that will help other cancer patients.

Mass General Cancer Center is a pioneer of this personalized approach of matching drugs to molecular targets, known to “fuel tumor growth.” What MGH researchers have found, however, is that even those who initially respond to targeted drugs often develop resistance because the tumor finds a way to return with a vengeance. But in Mr. McGlone’s case, it’s as if the drug were custom-made for his tumor. And that is teaching his team of physician-researchers lessons that will help other cancer patients.

“We now know that two people’s cancers may share some major mutations but respond differently to therapy,” says Ryan Corcoran, MD, PhD, director of Translational Research at the Tucker Gosnell Center for Gastrointestinal Cancers. “What we’re trying to do is take personalized medicine a step further and treat each patient as an entirely different cancer.” This advance in understanding he calls “customized” cancer care.

Rescued from the Brink

In the United States, the incidence of cancers involving the lower esophagus and upper stomach like Mr. McGlone’s have recently increased more rapidly than any other type of cancer. Because it develops slowly and silently, it is often not diagnosed until it has spread beyond the stomach. Chemotherapy didn’t work for Mr. McGlone and though radiation therapy helped a bit, the cancer didn’t retreat.

From left, Eunice Kwak, MD, PhD, Ryan Corcoran, MD, PhD, and Theodore Hong, MD
From left, Eunice Kwak, MD, PhD, Ryan Corcoran, MD, PhD, and Theodore Hong, MD.

“My prospects weren’t looking good,” says the 67-year-old resident of Hanover, Massachusetts. “It was 2011 and there was not much chance of me seeing 2012.”

Dr. Kwak offered him a drug she and her colleagues were testing for its ability to target a gene abnormality called MET amplification, an increase in the number of copies of that gene. From analyzing his tumor, she knew that he was among the 3-5 percent of those with stomach and esophageal cancer who have MET amplification.

When he returned to Mass General after a month on the therapy, everyone was excited. They showed him and his wife, Ruth, the PET scan. All the black spots where the cancer had been were gone. “No one could believe how fast it had worked,” he recalls. He comes to the Henri and Belinda Termeer Center for Targeted Therapies every month and is scanned every other month. All scans have been clear. He is extremely grateful for the care he receives there, including his dedicated nurse Susan Jaster, RN.

Enjoying Two Grandchildren

Whereas before Mr. McGlone could barely swallow, “now I can eat just about anything.” He may not have the strength and stamina he once had, but he’s able to enjoy his two grandchildren and family visits to New Hampshire. “I focus on the good part that I’m still around,” he says.

“We’re observing that people’s tumors keep changing over time and we have to keep tailoring our treatment to keep up with the changes,” Dr. Kwak reports.

Not everyone on the drug had the same dramatic response, Dr. Kwak points out. For some it didn’t work at all and for others it stopped working after a year or two, though they all also had MET amplification.

“Our subsequent work has been to understand why,” she says. To find answers, she, Dr. Corcoran and radiation oncologist Theodore Hong, MD, have been collaborating with John Iafrate, MD, PhD, director of Mass General’s Translational Research laboratory. “We’re observing that people’s tumors keep changing over time and we have to keep tailoring our treatment to keep up with the changes,” Dr. Kwak reports.

A careful molecular analysis of these patients’ tumors found that almost half of those with MET-amplified gastric and esophageal cancers also had another amplified cancer gene, HER2 or EGFR. “By targeting both MET and HER2 together, for example, we can get a tremendous response for those patients with both,” she says.

Customized Cancer Care

The researchers are now better able to keep up with tumor changes by using a new technique that only requires a blood sample, not a surgically removed biopsy of the tumor. Through monthly blood draws, they can monitor tiny amounts of tumor DNA that dying cancer cells shed into the bloodstream. They’ve found that patients develop not just one but several simultaneous mechanisms of resistance to therapy. As more is learned, they’ll be able to anticipate and prevent resistance with the appropriate drugs.

For more information on how you can support these translational research efforts to help more patients like Joseph McGlone, please contact us.