Interdisciplinary Initiatives Program Round 11 - 2022
Project Investigators:
Fan Yang, Orthopaedic Surgery and Bioengineering
Christina Curtis, Medicine (Oncology) and Genetics
Joy Wu, Medicine (Endocrinology, Gerontology, & Metabolism)
Abstract:
Metastasis is the leading cause of death in cancer patients. Bone is the most frequent metastatic site in breast cancer, the leading cancer that affects women. There is currently no cure once breast cancer spread to bone. The current standard experimental models for cancer research rely on mouse models or 2D culture. Mouse models are most physiologically relevant, but are costly, slow, and impractical for drug screening. While 2D culture is affordable and easy for drug screening, it lacks matrix cues and 3D architecture, thus not suitable to study cancer metastasis. Furthermore, no previous studies have integrated 3D bone metastasis model with patient-derived xenograft cells to reflect the heterogeneity of this disease. To improve the treatment outcomes of bone metastasis, it is critical to understand why breast cancer cells preferentially invade to bone tissues, and how cancer cells destroy bone after metastasis.
To fill in these critical gaps, here we propose to engineer a 3D in vitro breast cancer-bone metastasis model that mimics key clinical features including bone-specific metastasis and cancer- induced dysregulated bone remodeling. This model leverages on a spatially patterned, 3D tissue engineered cancer metastasis model invented by the PI’s lab, and will benefit from a new collaboration among a team of basic and clinician scientists. Our team has shared research interest in breast cancer and bring in complimentary expertise from biomaterials, tissue engineering, cancer biology, computational modeling, sequencing, drug discovery and breast cancer patients. The outcomes of the proposed work would establish an experimental model with optimized niche cues that mimics key clinical features of breast cancer-bone metastasis and patient heterogeneity. Such tool may advance our understanding of why breast cancer cells metastasize to bone, and facilitate discovery of novel drugs with significantly reduced time and cost.
