Hackensack University Medical Center Hackensack, New Jersey
Associate Member, Center for Discovery and Innovation Associate Professor, Department of Medical Sciences, Hackensack Meridian School Center for Discovery and Innovation Hackensack Meridian Health Adjunct Associate Professor, Department of Oncology Georgetown University School of Medicine, Lombardi Comprehensive Cancer Center
Identifying innovative approaches to improve response to therapies for triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is an extremely aggressive and heterogeneous disease. It accounts for 15-20 percent of all diagnosed breast cancers, and affects young women, particularly African Americans and women with germline BRCA mutations. Although chemotherapy is an effective therapy against TNBC, only 35-40 percent of patients respond to chemotherapy and the majority progress to metastatic disease within three years after diagnosis. There are few targeted therapies for TNBC, making the development of novel and personalized therapies an urgent need. The discovery that the composition of the gut and tumor microbiome, which consist of tens of trillions of bacteria, can influence whether or not a patient responds to chemotherapy prompted Dr. Feinman and her colleagues to ask if certain types of gut and tumor bacteria increase the efficacy of neoadjuvant chemotherapy by re-activating the patient’s immune system. They aim to identify novel microbiota-associated biomarkers that predict poor outcome—this could lead to the development of personalized microbial-based therapies that harness the immune system of TNBC patients to effectively defeat this disease.
Dr. Feinman and her team have assessed baseline compositions of the gut microbiome in tumor biopsies from patients with TNBC prior to and after treatment with standard of care neoadjuvant (presurgical) chemotherapy (NAC). Analysis reveals that the composition of the microbiome is predictive of NAC outcome in these patients. Preliminary results showed that the pre-existing composition of immune cells in the tumor microenvironment also influences patient response to NAC. They continue to enroll patients at multiple participating clinical sites.
Ongoing analyses of gut and tumor bacteria will determine correlations with patient immune response and outcome. In addition, Dr. Feinman and her team designed a staining method to visualize the spatial distribution of cells in the tumor microenvironment. They are employing this method to characterize the density and spatial relationship between TNBC tumor cells and specific immune cells. Through these studies, Dr. Feinman hopes to identify novel microbiota biomarkers that predict which patients are not likely to respond to neoadjuvant chemotherapy. She will build on this work to develop microbiota-centered interventions that can overcome resistance to chemotherapy and immunotherapy and improve outcomes for patients with this aggressive breast cancer.
Rena Feinman, PhD is an Associate Scientist in the Department of Research and Member of the John Theurer Cancer Center at Hackensack University Medical Center. She received her PhD in the Department of Microbiology at the New York University School of Medicine and pursued her postdoctoral fellowship at Memorial Sloan Kettering Cancer Center.
While on faculty at the Myeloma Institute for Research and Therapy in Little Rock, Arkansas, Dr. Feinman’s laboratory identified NFkappaB, a master regulator of immune and inflammatory responses, as a therapeutic target and predictive factor in clinical response to dexamethasone and immunomodulatory-based therapies in multiple myeloma patients.
Until 2013, Dr. Feinman was an Assistant and Associate Professor of Surgery at Rutgers-New Jersey Medical School. Her research investigated how hypoxia-inducible factors (HIF) and toll-like receptor signaling triggered intestinal inflammation during shock and critical illness led to the development of systemic inflammatory response syndrome and multiple organ failure.
Dr Feinman’s current research examines the influence of the gut microbiome in modulating anti-tumor immune responses in high-risk multiple myeloma. In collaboration with Dr. Leslie Montgomery, Dr. Feinman is working to identify novel gut flora-associated biomarkers that predict response to chemotherapy, disease-free survival, and overall survival in newly diagnosed TNBC patients.
2017
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