Elizabeth Comen, MD

Understanding how nerves regulate and promote breast cancer metastasis.

Impact

Cancer cells create a complex environment around themselves, the tumor microenvironment, that helps them grow and spread to other parts of the body. Nerves in tumors were previously thought to be passive, simply providing routes for cancer cells to move along. Recently, studies have shown that nerves can promote tumor formation in some cancers. More innervation in these tumors is linked to higher chances of recurrence and poorer survival rates. Drs. Comen and Tavazoie have uncovered a specific, targetable pathway by which tumors recruit nerve fibers to fuel their own spread, one that can potentially be blocked using a drug already approved and safe for use in patients.

Progress Thus Far

Drs. Comen and Tavazoie have discovered that breast tumors are frequently innervated by sensory nerves, and that more nerve involvement is linked to a greater likelihood of the cancer spreading. When the team removed these tumor-associated nerves, tumor growth slowed and metastasis to the lungs was significantly reduced, confirming that nerves actively drive cancer spread. The team went on to identify the specific molecular signal nerves use to communicate with cancer cells, and found that blocking this signal with an existing, FDA-approved drug suppressed tumor growth and metastasis in a model system. These findings were further supported by a large population study showing that patients who had received this drug for unrelated reasons had significantly fewer cancer recurrences. The team also discovered that tumor-associated nerves become active in distant organs, such as the lungs, even before cancer cells arrive there, suggesting nerves may help prepare distant sites for the cancer’s arrival.

What’s next

Drs. Comen and Tavazoie will investigate the small cancer cell subpopulation that is drives this nerve-driven signal in order to identify which patients are most likely to benefit from targeting this pathway. They will also study at what point during metastatic progression nerves have the greatest impact, and whether immune cells play a role in this process. Finally, having found that tumor-associated nerves in the lung become active before metastases form, the team will work to identify the specific signals these nerves release to help prepare the lung for incoming cancer cells.