Researchers in the lab of Alexander Birbrair, PhD, discovered that nerves play a key role in how melanoma can spread throughout the body. Now, his team is looking at the exact methods this deadly skin cancer uses to talk with nerves to develop new targeted cancer treatments to interrupt it. One promising idea could involve FDA-approved migraine medication.
Research led by Alexander Birbrair, PhD, shows that advanced melanoma exploits the nervous system to spread throughout the body.
Now, his team is looking at the exact mechanisms those tumors and nerves use to communicate so they can develop treatments to interrupt it. Their research so far suggests an existing FDA-approved migraine drug could be one potential treatment against melanoma, the deadliest form of skin cancer.
“Our ultimate goal is to learn how to 'hack' this communication network,” said Birbrair, a UW Carbone Cancer Center researcher and assistant professor of dermatology at UW School of Medicine and Public Health.
“If we can map exactly how the nerves are sending these fertilizer signals to the tumor, we can figure out how to cut the wire.”
An understudied gap
Birbrair’s research is part of an emerging field combining neuroscience with cancer biology. He recently was awarded more than $5 million in federal funding to advance his lab’s work.
The body’s central nervous system includes the brain and spinal cord, and it’s the processing center for sensory information and bodily functions. Neurons are the main cells of the nervous system, and they use electrical or chemical signals to communicate throughout the body.
The role of neurons in cancer progression has been understudied. Traditional methods that pathologists use to colorize cancer tissue samples for study left neurons “invisible” under the microscope for several years.
“We focus on melanoma because it is incredibly aggressive and deeply embedded in the skin, which is packed with nerve endings,” Birbrair said. “It is the perfect place to study how the nervous system and cancer interact.”
His lab showed that pain-sensing nerves actually grow directly into areas where melanoma is developing. Preclinical studies showing that “turning off” those specific nerves in study mice via gene editing kept the cancer from spreading.
“That 'eureka' moment proved that nerves aren't just innocent bystanders in the body. They are actively communicating with the cancer,” Birbrair said.
His lab is now closely examining several components of this communication to see where targeted treatment strategies could be developed to interrupt it.
Migraine drug promising
So far, his team has discovered that one type of neuropeptide that signals cancer cells to migrate and form new blood vessels is the same neuropeptide associated with migraines.
“When we found this signal was very important for the progression of metastatic melanoma, there are also luckily already eight FDA-approved migraine drugs that can block this signaling,” he said.
His lab has already done preclinical research with one of these drugs, and it successfully reduced the spread of melanoma tumors in the lungs of mouse models. He is now working with fellow UW Carbone researcher and medical oncologist Dr. Vincent Ma to launch a clinical trial testing this approach.
“If this works, we could bypass years of standard drug development and get a safe, effective new treatment into the hands of oncologists and patients much, much faster,” he said.
Birbrair’s team also collaborates with fellow UW Carbone researchers Dr. Paul Sondel; Nihal Ahmad, PhD; Vijay Setaluri, PhD; Justin Wolter, PhD; Sean McIlwain,PhD; Philippos Tsourkas, PhD; and Kevin Eliceiri, PhD.