Hit Me With Your Best Shot

Duke Cancer Institute physician Brent Hanks, MD, PhD, is studying patient tumors to reveal the genetic changes that happen when melanomas win a battle and become resistant to immunotherapy treatments.

In the last couple of years, patients with advanced melanoma have gained an ally in their fight against the disease, in the form of several different immunotherapies­—treatments that help the body's own immune system attack cancer. You may have heard of ipilimumab (Yervoy), which was approved in 2014 by the Food and Drug Administration to treat metastatic or inoperable melanoma. Clinical trials at Duke helped lead to that approval. There is also nivolumab (Opdivo), and pembrolizumab (Keytruda). These are all checkpoint inhibitors, which are drugs that remove the "brakes" that cancer can put on the body's immune system.

"The responses have been great with these new agents, and they have received a lot of media attention," says Duke medical oncologist April Salama, MD. "But we are only beginning to understand the complexities of why some patients benefit and others don't."

Brent Hanks, MD, PhD, points out that only about 35 percent of patients respond to these treatments. "That means that 65 percent of patients are not responding," Hanks says. "We want to understand why that is."

So Hanks is studying tumor tissue and circulating tumor cells from a small number of Duke patients being treated with one of these immunotherapies, to discover the genetic changes that happen in their tumors.

In many patients, treatment with immunotherapy leads to the disease becoming stable; the metastatic disease is neither decreasing nor growing, but has come to a standstill.  "We believe that during that period of time there is an ongoing battle between the tumors and the immune system," Hanks says. "We are trying to understand the pathways that the tumor uses to avoid detection and destruction."

Understanding those evasion tactics could lead to new drugs to prime the immune system for the fight, or to predictive biomarkers that could alert doctors when the immune system is starting to lose to the cancer.  

Hanks uses a mouse model to help guide his studies of human tumors. "There are so many different melanoma variations in the human population that it makes it really difficult to home in on a single factor that could be important," Hanks says. "We have these mice that develop melanoma; it looks like human melanoma and behaves like it genetically." he says. After treating the mice with one of the currently approved immunotherapies, he studies the resulting changes. "We try to understand the genetic changes in those tumors to see if we can identify certain pathways to focus on in the human specimens."

Patients participate in this small study by invitation. To learn more, visit Clinical Trials.