Titles and Affiliations
Leon Hess Professor
Head, Elizabeth and Vincent Meyer Laboratory of Systems Cancer Biology
Director, Black Family Metastasis Center
Senior Attending Physician
The Rockefeller University
Attending Physician
Member, BCRF Scientific Advisory Board
Research area
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. Tavazoie and Comen 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. Tavazoie and Comen 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. Tavazoie and Comen 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.
Biography
Sohail Tavazoie, MD, PhD graduated from the University of California at Berkeley and completed an MD-PhD program at Harvard-MIT, followed by residency training in Internal Medicine at Brigham & Women’s Hospital at Harvard and medical oncology and postdoctoral fellowship training at Memorial Sloan Kettering Cancer Center. In 2009, he was recruited to The Rockefeller University as Head of the Laboratory of Systems Cancer Biology. In addition to his laboratory work, Dr. Tavazoie is an attending medical oncologist at Memorial Sloan Kettering Cancer Center.
His laboratory studies the roles that small-RNAs play in regulating cancer metastasis. Small-RNAs, also called microRNAs, have the ability to block the expression of genes. During his postdoctoral work in Joan Massague’s laboratory at MSKCC, Dr. Tavazoie discovered the first set of non-coding RNAs that act as suppressors of metastasis. These small RNAs were found to be shut off in breast tumors that metastasized. His lab at The Rockefeller University has shown that each of these small-RNAs block the expression of distinct sets of genes that enable breast cancer cells to metastasize. These genes were found to enhance the invasive capacity of breast cancer cells as well as their ability to recruit endothelial cells. His laboratory studies the mechanisms by which these small-RNAs and the genes they regulate control metastasis. By better understanding the molecular pathways that govern metastatic progression, he hopes to enable the development of novel therapeutics that prevent the formation and progression of breast cancer metastasis.
