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Proceedings Paper

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

Paper Details

Date Published: 13 March 2013
PDF: 6 pages
Proc. SPIE 8568, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXII, 85680R (13 March 2013); doi: 10.1117/12.2010730
Show Author Affiliations
Jonathan P. Celli, Univ. of Massachusetts Boston (United States)
Wellman Ctr. for Photomedicine, Massachusetts General Hospital, Harvard Medical School (United States)
Ljubica Petrovic, Univ. of Massachusetts Boston (United States)
Iqbal Massdodi, Wellman Ctr. for Photomedicine, Massachusetts General Hospital, Harvard Medical School (United States)
Imran Rizvi, Wellman Ctr. for Photomedicine, Massachusetts General Hospital, Harvard Medical School (United States)
Tayyaba Hasan, Wellman Ctr. for Photomedicine, Massachusetts General Hospital, Harvard Medical School (United States)


Published in SPIE Proceedings Vol. 8568:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXII
David H. Kessel; Tayyaba Hasan, Editor(s)

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