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Proceedings Paper

Biologically relevant 3D tumor arrays: treatment response and the importance of stromal partners
Author(s): Imran Rizvi; Jonathan P. Celli; Feng Xu; Conor L. Evans; Adnan O. Abu-Yousif; Alona Muzikansky; Stefan A. Elrington; Brian W. Pogue; Dianne M. Finkelstein; Utkan Demirci; Tayyaba Hasan
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Paper Abstract

The development and translational potential of therapeutic strategies for cancer is limited, in part, by a lack of biological models that capture important aspects of tumor growth and treatment response. It is also becoming increasingly evident that no single treatment will be curative for this complex disease. Rationally-designed combination regimens that impact multiple targets provide the best hope of significantly improving clinical outcomes for cancer patients. Rapidly identifying treatments that cooperatively enhance treatment efficacy from the vast library of candidate interventions is not feasible, however, with current systems. There is a vital, unmet need to create cell-based research platforms that more accurately mimic the complex biology of human tumors than monolayer cultures, while providing the ability to screen therapeutic combinations more rapidly than animal models. We have developed a highly reproducible in vitro three-dimensional (3D) tumor model for micrometastatic ovarian cancer (OvCa), which in conjunction with quantitative image analysis routines to batch-process large datasets, serves as a high throughput reporter to screen rationally-designed combination regimens. We use this system to assess mechanism-based combination regimens with photodynamic therapy (PDT), which sensitizes OvCa to chemo and biologic agents, and has shown promise in clinic trials. We show that PDT synergistically enhances carboplatin efficacy in a sequence dependent manner. In printed heterocellular cultures we demonstrate that proximity of fibroblasts enhances 3D tumor growth and investigate co-cultures with endothelial cells. The principles described here could inform the design and evaluation of mechanism-based therapeutic options for a broad spectrum of metastatic solid tumors.

Paper Details

Date Published: 2 March 2011
PDF: 14 pages
Proc. SPIE 7886, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XX, 788609 (2 March 2011); doi: 10.1117/12.875892
Show Author Affiliations
Imran Rizvi, Wellman Ctr. for Photomedicine, Massachusetts General Hospital (United States)
Jonathan P. Celli, Wellman Ctr. for Photomedicine, Massachusetts General Hospital (United States)
Feng Xu, Brigham and Women's Hospital (United States)
Conor L. Evans, Wellman Ctr. for Photomedicine, Massachusetts General Hospital (United States)
Adnan O. Abu-Yousif, Wellman Ctr. for Photomedicine, Massachusetts General Hospital (United States)
Alona Muzikansky, Massachusetts General Hospital (United States)
Stefan A. Elrington, Wellman Ctr. for Photomedicine, Massachusetts General Hospital (United States)
Brian W. Pogue, Dartmouth College (United States)
Dianne M. Finkelstein, Massachusetts General Hospital (United States)
Utkan Demirci, Brigham and Women's Hospital (United States)
Tayyaba Hasan, Wellman Ctr. for Photomedicine, Massachusetts General Hospital (United States)


Published in SPIE Proceedings Vol. 7886:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XX
David H. Kessel; Tayyaba Hasan, Editor(s)

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