Sandra and Edward H. Meyer Professor
Chair of Radiation Oncology
Co-Director, Breast Cancer Research
Associate Director, NYU Cancer Institute
NYU School of Medicine
New York, New York
Radiation therapy (RT) directed at a tumor causes a series of specific danger signals that activate the immune system around the tumor. Experiments led by Drs. Formenti and Demaria found that RT enhanced the effect of an antibody blocking the immune suppressor protein CTLA-4 in an experimental model of metastatic breast cancer. Importantly, the resulting immune response was not only effective against the primary irradiated tumor, but also prevented lung metastases. In other words, it vaccinated the host against the irradiated tumor and its metastases. This finding is very relevant clinically, since it could be rapidly adopted to treat metastatic cancer patients. In their BRCF research, the investigators are focused on identifying combinations of therapeutic antibodies to neutralize immune-suppressive molecules in the tumor to allow efficient immune response to subsequent radiotherapy. In the last year the research team reported a significant reduction in tumor growth in a model of metastatic breast cancer when antibody-targeted inhibition of two different immune-suppressive molecules was used in combination with radiotherapy. In the coming year they will compare the results obtained with antibodies and newly developed small molecule inhibitors (SMI) to provide necessary data for moving this strategy forward in patients. Preliminary results suggest that the strategy of blocking multiple selected immune inhibitory targets in combination with radiotherapy has the potential to unleash powerful anti-tumor responses and improve the outcome of metastatic breast cancer in the near future.
Dr. Formenti is the Sandra and Edward H. Meyer Professor and Chairman of the Department of Radiation Oncology at NYU since1999. She also is the Associate Director for Clinical Research and the co-Leader of the Breast Cancer Research Program of the NYU Cancer Institute.
A native of Milan, Italy, she graduated medical school and did medical oncology training at the Università degli Studi (summa cum laude), before coming to USC to work in the laboratory of Dr. Malcolm Mitchell in cancer immunology. After an ACS fellowship in AIDS and lymphoma, she completed a residency in radiation oncology at USC.
A prolific researcher (greater than 150 publications), Dr. Formenti has pioneered the use of concurrent chemo-radiation in locally advanced breast cancer (LABC). Her research has been consistently funded by NIH, ACS, BCRF and Komen, and culminated in 2005 with a Center of Excellence Award from the Department of Defense Breast Cancer Research Program to study the biology and outcome of international LABC (Mexico, India, and S. Africa).
Inspired by clinical observations, Dr. Formenti has demonstrated in preclinical models how ionizing radiation can result in immunogenic cell death, converting the primary tumor into an individual in vivo vaccine. Another research focus is reducing late cardiovascular toxicity of breast cancer radiotherapy with a prone technique that excludes heart and lung. Recognized by high impact journals like JAMA and NEJM, her research has resulted in a US patent and a CME course offered since 2007, with wide international outreach and training.