Organovo -- >>> AACR Presentation Abstract
>>> Abstract Number: 2034
Presentation Title: Development of 3D bioprinted human breast cancer for in vitro drug screening
Presentation Time: Monday, Apr 07, 2014, 1:00 PM - 5:00 PM
Location: Hall A-E, Poster Section 5
Poster Board Number: 18
Author Block: Shelby M. King, Sharon C. Presnell, Deborah G. Nguyen. Organovo, Inc., San Diego, CA
Abstract Body: As breast cancer is a disease of multiple cell types in which the growth, invasion, and metastasis of epithelial carcinomas is heavily influenced by the surrounding cell types, screening of anti-cancer compounds using cancer cell lines grown in 2D often overestimates drug potency. Regulatory agencies are currently seeking improved preclinical oncology models to overcome hurdles to efficient drug development, including bridging the gap between the use of 2D cell lines and 3D animal models. One way to more accurately determine the effects of anti-cancer compounds is through the use of cancer tissue models that incorporate stromal cells of the tumor microenvironment. Breast stroma, composed of fibroblasts, endothelial cells, and adipocytes, plays a key role in the process of carcinogenesis and metastasis. These cell types secrete extracellular matrix, growth factors, and hormones that affect how therapeutic agents access and target cancer cells. We have used Organovo’s NovoGen BioprintingTM Platform to develop a model of human breast cancer in which a core of breast cancer cells is surrounded by a physiologically-relevant stromal milieu consisting of adipocytes, mammary fibroblasts, and endothelial cells. This system has several advantages over current screening tools, including the ability to simultaneously measure the effects of small molecules on cancer cells as well as different cell types in the breast microenvironment. Histological analyses of bioprinted neotissues demonstrated that they were stable and viable for at least 14 days in culture and characterized by interaction between stroma and carcinoma compartments. Incorporation of endothelial cells into the 3D neotissue led to the formation of robust microvascular networks. Breast cancer neotissues were fabricated directly into multi-well plates and used to establish biological response profiles to the standard chemotherapeutic agents cisplatin, paclitaxel, methotrexate, and tamoxifen. The cytotoxic effects of chemotherapeutic drugs on specific cell types within the neotissues were assessed biochemically and histologically. he response of the 3D breast cancer neotissues to chemotherapeutic gents was compared to the response of 2D breast cancer cell lines to determine he relative efficacy of compounds in 2D versus 3D. This model can be used to screen new anti-cancer therapeutics in the context of the in vivo-like microenvironment, leading to enhanced efficiency and accuracy of the drug development process.
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