Abstract B44: Mapping, targeting, and eliminating therapeutically unresponsive ovarian cancer with high content imaging and photodynamic therapy
Authors: Hung Hsin-I , Klein Oliver J. , Jung Yookyung , Kulkarni Kashmira S. , Rueda Bo R. , Foster Rosemary , Evans Conor L. 
Published: August 2014

Abstract
Ovarian cancer is the 5th most common cancer among women, in which epithelial ovarian cancer (EOC) is the most common type, accounting for 90% of cases. Currently, the standard treatment for ovarian cancer is surgical debulking followed by chemotherapy. Although initially EOC patients are highly responsive to standard platinum-derived chemotherapy, the majority of cancer patients will eventually relapse and experience chemoresistance. In spite of numerous efforts to improve EOC treatment, the five-year overall survival rate is still disappointing at 30%. It is therefore necessary to examine the fundamental causes of treatment resistance and use this information to design new therapeutic strategies. Recently, the concept of tumor-initiating cells and their supporting tumor microenvironment has been proposed as potential targets for cancer treatment due to their observed chemoresistance and ability to repopulate tumors. These cells are proposed to reside deep within tumors, potentially in oxygen-deprived environments. We recently observed that a light-based treatment modality known as photodynamic therapy (PDT) may be uniquely suited to targeting and eliminating this cellular population. PDT applies a light activated drug (photosensitizer) to selectively target and kill cancer cells through generation of reactive oxygen species (ROS), making it an attractive alternative cancer treatment modality with the potential to overcome adaptive therapeutic resistance. Characteristics of PDT, including the direct destruction of cellular organelles, selective tumor accumulation, and photochemistry-driven tumor killing mechanism give PDT advantages over traditional chemotherapy and radiotherapy. We have found that a lysosome targeted photosensitizer known as EtNBS specifically localizes and accumulates into the acidic and hypoxic tumor microenvironment in 3D cultures to successfully kill otherwise unresponsive cellular populations. EtNBS-mediated PDT is thus a potential modality in treating tumor initiating cells. In addition, the quantitative and label-free optical coherence tomography (OCT) imaging modality has recently been demonstrated to provide real time information regarding tumor tissue structure and therapeutic dynamics, making it a potential tool to study tumors and their associated change during the course of tumor development and treatment. Here, we utilized a 3D in vitro metastatic ovarian cancer culture model, with an oxygen sensor and OCT imaging as a combinational platform to study tumor initiating cells and the effects of their associated tumor microenvironment on therapeutic response under standard and EtNBS-PDT treatment. By mapping tumor response with this integrated platform, this work represents a mechanism- based targeted approach that will hopefully enable the identification of cellular targets to overcome disease relapse and adaptive chemoresistance.
Citation Format: Hsin-I Hung, Oliver J. Klein, Yookyung Jung, Kashmira S. Kulkarni, Bo R. Rueda, Rosemary Foster, Conor L. Evans. Mapping, targeting, and eliminating therapeutically unresponsive ovarian cancer with high content imaging and photodynamic therapy. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B44.