Overcoming therapeutic resistance in pancreatic cancer is not a simple mix of PDT and
chemotherapy: Evaluation of PDT-chemotherapy combinations in 3D tumor models

Jonathan P. Celli; Ljubica Petrovic; Iqbal Massdodi; Imran Rizvi; Tayyaba Hasan

doi:10.1117/12.2010730

13 March 2013 Overcoming therapeutic resistance in pancreatic cancer is not a simple mix of PDT and chemotherapy: Evaluation of PDT-chemotherapy combinations in 3D tumor models

Jonathan P. Celli, Ljubica Petrovic, Iqbal Massdodi, Imran Rizvi, Tayyaba Hasan

Author Affiliations +

Proceedings Volume 8568, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXII; 85680R (2013) https://doi.org/10.1117/12.2010730
Event: SPIE BiOS, 2013, San Francisco, California, United States

Abstract

The dismal survival statistics for pancreatic cancer are due in large part to the notoriously poor response of these tumors to conventional therapies. Here we examine the ability of photodynamic therapy (PDT), using the photosensitizer verteporfin to enhance of the efficacy of traditional chemotherapy agents and/or eradicate populations that are nonresponsive to these agents. Using an in vitro 3D tumor model of pancreatic cancer combined with an imaging-based methodology for quantifying therapeutic response, we specifically examine PDT combination treatments with gemcitabine and oxaliplatin. We show that our 3D cell culture model recapitulates a more clinically-relevant dose response to gemcitabine, with minimal cytotoxic response even at high doses. The same cultures exhibit modest response to PDT treatments, but are also less responsive to this modality relative to our previous reports of monolayer dose response in the same cells. In combination we found no evidence of any enhancement in efficacy of either PDT or gemcitabine treatment regardless of dose or sequence (PDT before gemcitabine, or gemcitabine before PDT). However, when oxaliplatin chemotherapy was administered immediately after treatment with 2.5J/cm² verteporfin PDT, there was an observable enhancement in response that appears to exceed the additive combination of either treatment alone and suggesting there may be a synergistic interaction. This observation is consistent with previous reports of enhanced efficacy in combinations of PDT with platinum-based chemotherapy. The contrast in results between the combinations examined here underscores the need for rational design of mechanism-based PDT combinations.

Citation Download Citation

Jonathan P. Celli, Ljubica Petrovic, Iqbal Massdodi, Imran Rizvi, and Tayyaba Hasan "Overcoming therapeutic resistance in pancreatic cancer is not a simple mix of PDT and chemotherapy: Evaluation of PDT-chemotherapy combinations in 3D tumor models", Proc. SPIE 8568, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXII, 85680R (13 March 2013); https://doi.org/10.1117/12.2010730

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