McGowan Institute for Regenerative Medicine affiliated faculty member Shilpa Sant, PhD, Assistant Professor of Pharmaceutical Sciences, has received a 7-year R37 MERIT Award from the National Cancer Institute (NCI), NIH, for her project entitled, “Three-dimensional organoid models to study breast cancer progression.” This grant is funded by the NCI under the Cancer Tissue Engineering Collaborative (TEC) Research Program that aims to support the development and characterization of state-of-the-art biomimetic tissue-engineered technologies for cancer research. The total funding for the first 5 years is $2.7 million.
The funded proposal aims to develop a three-dimensional in vitro organoid model that recapitulates key hallmarks of progression of non-invasive breast cancer to invasive disease. The goal is to discover key hypoxia-induced factors involved in initiation, maintenance, and spatial distribution of invasive breast cancer cells using 3D tumor organoid model and computational modeling approaches. Specifically, the proposal will use integrated experimental and computational approaches, coupled with deep learning-based image analysis, to delineate how hypoxia, tumor secretome, and intracellular signaling networks work together to induce the migratory phenotype and drive progression to invasive disease.
Currently, there are no prognostic biomarkers that can reliably predict the risk of progression from non-invasive to invasive breast cancer, leading to over-treatment of patients that are not at risk. The successful development of the proposed 3D organoid model will provide answers to two fundamental questions in the progression of invasive breast cancer:
- What causes some non-invasive breast cancer cells to become migratory and develop into invasive tumors?
- How and where does the migratory phenotype emerge?
The mechanistic understanding gained from these studies will improve diagnosis, prevent patient overtreatment, and lead to the development of treatment strategies to arrest invasion at the pre-invasive stage.
Co-principal investigators on the project include:
- Jianhua Xing, PhD, Associate Professor, Computational and Systems Biology
- Vera Donnenberg, PhD, Associate Professor of Cardiothoracic Surgery and Pharmaceutical Sciences, and McGowan Institute for Regenerative Medicine faculty member
- Simon Watkins, PhD, Distinguished Professor and Director of the Center for Biologic Imaging, and McGowan Institute for Regenerative Medicine affiliated faculty member
- Priscilla McAuliffe, MD, PhD, Assistant Professor of Surgery, University of Pittsburgh School of Medicine
Dr. Sant also holds appointments in the Department of Bioengineering and UPMC-Hillman Cancer Center.