Stuart A. Aaronson, MD
Jack and Jane B. Aron Professor
Founding Chair Emeritus
Department of Oncological Sciences
Mount Sinai School of Medicine
New York, New York
2013-2014 BCRF Project:
(The Delta Air Lines Award)
Dr. Aaronson continues his work on identifying breast cancer biomarkers and his research using a Wnt autocrine transforming mechanism in triple negative breast tumors to develop novel therapies for these tumors. His team recently established a human inflammatory breast cancer line, whose characterization could provide insights into specific therapies for this aggressive breast malignancy. They also identified aberrant epigenetic regulation of erbB2 in HER2-positive (HER2+) subtype breast tumors. These findings provide better understanding of how this gene becomes overexpressed in breast cancers and identify possible new therapeutic targets in erbB2 positive breast cancers.
Dr. Aaronson’s team is working to identify breast cancer biomarkers and exploit their findings of a Wnt autocrine transforming mechanism in triple negative human breast tumors. They recently showed that Wnt activation confers increased invasive properties and survival advantages to such tumor cells, and their efforts to develop small molecule inhibitors of this pathway led to a manuscript in revision describing one new compound. They demonstrated further that a human inflammatory breast cancer line being characterized by their laboratory secretes molecules that stimulate tumor growth through influences on the tumor microenvironment, providing insights into potential new therapies for this aggressive breast malignancy. They also published a study demonstrating aberrant epigenetic regulation of erbB2 in erbB2 overexpressing and amplified breast tumors, identifying new therapeutic targets in erbB2 positive breast cancers.
At the National Cancer Institute as Chief, Laboratory of Cellular and Molecular Biology, Dr. Stuart Aaronson’s early investigations of mammalian transforming retroviruses led to the discovery of the first normal function of an oncogene and demonstration that genes encoding growth factors could be transforming (sis/PDGF). He and his colleagues subsequently discovered ErbB2 as an erbB related gene amplified in a primary human breast cancer, and genes for other growth factor signaling molecules, that could also be activated as oncogenes in human malignancies. Dr. Aaronson’s research has contributed to novel cancer drugs including Herceptin, which targets ERBB2, and KGF/FGF7, discovered by this team as a unique epithelial cell acting growth factor, which became Kepivance, for treatment of cancer therapy associated mucositis. Other discoveries, including erbB3, PDGFR alpha, and HGF as the ligand for MET, have also led to agents currently in clinical development as cancer therapeutics.
Dr. Aaronson joined Mount Sinai in 1993 and initiated studies of Wnt signaling with the goal of identifying novel Wnt activation mechanisms such as Wnt autocrine signaling in human tumors. His team identified and cloned cell surface acting Wnt antagonists, FRP and DKK1, established their mechanisms of action, and contributed to understanding of Wnt co-receptor activation. Using these and other approaches, they have established that autocrine Wnt signaling is a common mechanism of Wnt canonical pathway activation in human tumors ranging from epithelial malignancies including breast, ovarian, and non-small cell lung carcinomas, to a wide array of mesenchymally derived sarcomas. Dr. Aaronson has also identified novel p53 functions in cell stress responses and transcriptional mechanisms differentially regulating p53 growth arrest and apoptosis. He has published extensively on growth control and cancer, holds more than 50 patents, and has trained dozens of investigators, who are in academic positions, biotech/pharma, or head cancer centers/institutes in the US and abroad.