Big Ideas

Nikhil Wagle, M.D.

Breast cancer is the most common cancer diagnosis in American women. Through research, the medical world has built up an arsenal of tools to treat it in its early stages, and the prognosis can be favorable when breast cancer is detected early on. Yet, it’s frustrating we remain without a cure when it comes to advanced or metastatic breast cancer.  

Metastatic breast cancer is a cancer that has spread beyond the tissues of the breast. According to Nikhil Wagle, M.D., of the Dana-Farber Cancer Institute, about one fourth of people treated for breast cancer in its early stages will see a recurrence in a more advanced form – metastatic breast cancer. People diagnosed with metastatic breast cancer only live an average of three years, because most often the disease in its later stages has developed resistance to cancer therapies. This is where research becomes critical. 

Wagle’s work focuses on the resistance of advanced breast cancer cells and how to develop therapies that will enable us to defeat advanced breast cancer. His lab uses donated samples from patients with advanced breast cancer. “So much of the research we do is empowered by the participation of patients,” he said. He and his team analyze the patient samples to understand why the tumors become resistant and then develop therapies to get past resistance. The next step is to try these therapies on the patients. 

According to Wagle, there are approximately 150,000 people in the U.S. living with metastatic breast cancer, and 40,000 people die of it every year. This accounts for 14% of cancer deaths among women in the U.S. “People continue to get advanced breast cancer, and we need to find a cure. That’s what we think about every day,” he said. 

People diagnosed with metastatic breast cancer only live an average of three years, because most often the disease in its later stages has developed resistance to cancer therapies. This is where research becomes critical. 

Wagle credits the V Scholar Award for funding his research, which pinpointed one major mechanism that leads to treatment resistance. His lab was thus able to identify an existing drug that could overcome it. “I’m pretty hopeful about the progress that’s being made,” he said.  

Wagle’s lab found that some breast cancer tumors that become resistant to therapies targeting estrogen receptors do so because they develop a mutation in the gene called HER2. There is currently a drug in clinical trials that targets those mutations specifically and makes them sensitive to the treatment again. “The drug [already] exists, and we’ve identified that it might be particularly useful in this group of patients who develop resistance,” he said. “But this is just one example; there’s a lot more to discover. We’ve identified several [reasons for resistance], and we hope to identify several more.”  

Wagle’s goal is to figure out the whole map of resistance – the “Resistance Atlas” – so strategies to attack it in advanced cancer cells are developed and ultimately cure metastatic breast cancer. “That’s where I hope we’re headed,” he said.