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
Co-Investigator: Sandra Demaria, MD, NYU School of Medicine, New York, NY
Research developments in cancer immunology have elucidated important mechanisms of resistance to rejection of human tumors by our natural self-defense system, the immune system. When radiotherapy targets a cancer it elicits a series of specific danger signals that alert the patient’s immune system about the tumor. Dr. Formenti’s group has first hypothesized a role for local radiotherapy as an adjuvant to cancer immunotherapy. A milestone in 2005 came from experiments from this group, in a laboratory model of metastatic breast cancer: an immunotherapy found to be ineffective when used alone induced therapeutically effective anti-tumor immunity when combined with tumor radiotherapy. Importantly, the resulting immune response rejected the primary irradiated tumor, and induced an immune response capable to also reject lung metastases outside of the radiation field. 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. Nevertheless, the optimal combination of immunotherapy and radiotherapy remains to be defined.
In 2013-2014, Drs. Formenti and Demaria will direct their efforts to identify combinations of therapeutic antibodies that will neutralize key immunosuppressive mediators in the tumor thus removing the main obstacles to the conversion of a growing tumor into an in situ vaccine by radiotherapy. The time is mature for a fast-track progress of the proposed strategy to clinical translation due to improved understanding of the regulation of anti-tumor immune responses, together with availability of therapeutic antibodies suitable for clinical use. Therefore, Drs. Formenti and Demariaplan to devote the first year to preclinical experiments and, depending on the results obtained, rapidly move to a clinical protocol that will translate their preclinical findings. If successful, this approach can be easily implemented at any radiotherapy facility and can be incorporated in the management of metastatic breast cancer in the near future.
Research developments in cancer immunology have elucidated important mechanisms of resistance to rejection of human tumors by our natural self-defense system, the immune system. Radiotherapy has shown the ability to convert a growing tumor into an in situ vaccine by releasing tumor antigens and generating an acutely inflamed environment. The NYU team’s preclinical experiments show that two key immunosuppressive factors are also induced in response to radiation and hinder the development of effective anti-tumor responses. Inhibition of each of these immunosuppressive factors improves immune-mediated control of the irradiated tumor and non-irradiated metastases, but tumors persist or recur. They will determine if concomitant neutralization of both immunosuppressive factors in the context of radiotherapy can induce stronger anti-tumor immunity that cures laboratory models with metastatic breast cancer. If successful, they will rapidly move to a clinical protocol that will translate their preclinical findings.
Silvia Formenti, MD, was appointed in 2000 as the first Sandra and Edward H. Meyer Chairman of the new Department of Radiation Oncology. Widely respected for her work in breast and cervical cancer, Dr. Formenti joined NYU from the University of Southern California, Keck School of Medicine in Los Angeles, where she was a tenured Associate Professor of both Radiation Oncology and Medicine. She has been a member of the Advisory Board to the NYU Breast Cancer Program since 1996.
Dr. Formenti, a native of Milan, Italy, attended medical school at the Universita degli Studi di Milano. She completed residencies in internal medicine and medical oncology followed by one in radiology and radiation oncology in Milan, before coming to the States to work at USC in Dr. Malcolm Mitchell's laboratory, funded by a grant from the Italian National Research Committee (CNR). After a year in the lab she returned to the clinic as an Audrey Meyer Mars American Cancer Society Fellow and worked with Dr. Robert Lukes and Dr. Alexandra Levine on AIDS and Lymphomas. She then elected to permanently transfer to this country and completed an internship in general medicine and a residency in radiation oncology, before joining the faculty at USC.
A prolific researcher, Dr. Formenti started with a 3-year ACS career development award and is currently principal or co-principal investigator on five multi-year peer-reviewed grants with more than $ 3 million in total funding. She has devoted her research career to the study of women's malignancies, with a particular focus on underserved patients and Latina women. She has pioneered the use of concurrent chemo-radiation in the neo-adjuvant (before surgery) setting of LABC, an ideal setting to explore associations of pre-treatment tumor molecular markers with the extent of pathological response (response in the removed surgical specimen) after chemo-radiation. This research has been consistently funded by the NIH and ACS. The translational component of this research consists of several collaborations with basic scientists to identify in the laboratory which original tumor molecular tumor marker might determine response to a specific treatment. In addition, at NYU, in collaboration with Dr. Sandra Demaria she is studying how chemo-radiation induced cell-death affects patient's immunity.
Finally, funded by a grant from the Department of Defense, she is studying the role of partial breast radiation with an accelerated regimen, 5 instead of 30 fractions. She is also the P.I. in two other studies investigating the role of intensity modulated radiation therapy (IMRT) as a tool to reduce the number of radiation sessions required to treat small breast cancers.
In addition to her role as Chairman of the NYU Department of Radiation Oncology, Dr. Formenti is currently the Associate Director for Clinical Research as well as the Leader of the Breast Cancer Research Program of the NYU Cancer Institute, where she oversees the clinical and research efforts of over 30 investigators.