5 March 2018 Cellular pH and PI3K signaling as determinants of Protoporphyrin IX conversion and ALA PDT response
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Abstract
ALA PDT is a FDA approved cancer treatment. The general model is that excess exogenous ALA is eventually converted to the active photosensitizer, PpIX, and accumulates PpIX to concentrations well above baseline. This accumulation, however, varies considerable from person to person and even intra-tumorally due to a high number of factors that are involved. Due to this there is an increasing desire to pair ALA PDT with other treatments to enhance the efficacy of PDT. This idea itself isn’t new as the labs of Bin Chen and Edward Maytin have a long history of using biology to enhance PpIX accumulation. The PI3K pathway is a long-studied cancer treatment target due to it being one of the most ubiquitous over expressed pathways in cancer and that many treatments have demonstrated enhanced efficacy upon PI3K inhibition. In this paper we show that the PI3K pathway inhibitor, LY294002, alters PpIX accumulation in cells (decreased for A431 and increases for Panc-1 and Panc-1 OR) and significantly increases the efficacy of ALA PDT in every case for both monolayer and spheroid cultures. Additionally, we show that PDT treatments using the nonendogenous photosensitizer, verteporfin, also have enhanced efficacy upon PI3K inhibition. Beyond the treatment synergy of PI3K inhibition and PDT, this work presents a cell pairing model that is perfect to study the previously, to our knowledge, undocumented connection between the PI3K pathway and PpIX accumulation.
Conference Presentation
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Michael Anderson, Michael Anderson, Hamid El-Hamidi, Hamid El-Hamidi, Jonathan Celli, Jonathan Celli, } "Cellular pH and PI3K signaling as determinants of Protoporphyrin IX conversion and ALA PDT response", Proc. SPIE 10476, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVII, 104760R (5 March 2018); doi: 10.1117/12.2283543; https://doi.org/10.1117/12.2283543
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