Exceptional responders: Why do some cancer drugs work for them and not others?

A female scientist reviewing a strip test in her hand
Some cancer patients respond so well to certain treatment when others do not that scientists are researching what makes them unique. Find out what they're learning about so-called exceptional responders, and how that may lead to advancements in cancer treatment.

When researchers conduct a clinical trial on a new cancer drug, the therapy often doesn’t work for a majority of patients. But sometimes, one particular patient responds so well that the cancer stops growing, or even disappears completely. Such patients are so unique that scientists have a special name for them: unicorns. Also known as exceptional responders, these outlier patients are now the subjects of intense research into why they show such positive responses when others don’t, and how the learnings may help other patients.

This is the holy grail of cancer treatment—finding what makes these patients unique. It’s the silver bullet that may help fight cancer in a specific patient.” - Arturo Loaiza-Bonilla, MD, MSEd, FACP - Chief of Medical Oncology and Medical Director of Research at our hospital in Philadelphia

A study sheds new light

In the past, if only one in 10 patients responded to a new drug, researchers assumed the therapy wasn’t effective for that cancer type and would discontinue that line of research. But a study published in 2012 changed conventional thinking on exceptional responders. The study noted that an advanced bladder cancer patient participating in a clinical trial had such an “impressive response” to a targeted therapy that she stood out starkly from the other 44 trial participants. So the researchers decided to dig deeper. After performing molecular testing on the DNA of the woman’s tumor, researchers discovered two genetic mutations that are uncommon in most bladder cancer patients. But when the mutations are present, they make the tumor more receptive to treatment. The study, the first to delve into the biology of an exceptional responder, prompted the National Cancer Institute to launch the Exceptional Responders Initiative, a pilot study focused on researching how specific genetic features in exceptional responders’ tumors could help advance cancer treatment.

Already, researchers have learned that between 10 percent and 20 percent of tumors in exceptional responders have unusually high numbers of genetic mutations, which may make the tumors more likely to respond to immunotherapy drugs. That means that identifying predictive biomarkers, or unique DNA mutations in the tumor cells of exceptional responders, may help researchers design drugs to target those same mutations in other patients’ tumor, regardless of where the tumor is located in the body. “We now know that when your tumor has a certain feature, you’re more likely to respond to immunotherapy, and you’re going to do much better because of that,” Dr. Bonilla says. “Patients have this advantage that they didn’t have before.”

How can advanced genomic testing help?

Armed with this new knowledge, experts are encouraging patients to talk to their doctor about advanced genomic testing if their cancer is not responding to standard-of-care treatments. “Patients need to be their own advocates,” Dr. Bonilla says. “When I’ve tested some patients who weren’t responding to chemotherapy, for example, I’ve found they have a specific DNA mutation in their tumor that meant they were a candidate for a specific type of immunotherapy drug, which we wouldn’t have known otherwise.” Testing the patients’ tumors has an added benefit for the world of research, and potentially, other patients,

Dr. Bonilla adds: The more biomarker testing researchers perform, the more exceptional responders the science community is likely to identify. “The more exceptional responders we study, the more we can tailor treatments to help more people,” Dr. Bonilla says.