It is increasingly evident that the most effective cancer treatments will involve interactive regimens that target multiple non-overlapping pathways, preferably such that each component enhances the others to improve outcomes while minimizing systemic toxicities. Toward this goal, we developed a combination of photodynamic therapy and irinotecan, which mechanistically cooperate with each other, beyond their individual tumor destruction pathways, to cause synergistic reduction in orthotopic pancreatic tumor burden. A three-way mechanistic basis of the observed the synergism will be discussed: (i) PDT downregulates drug efflux transporters to increase intracellular irinotecan levels. (ii) Irinotecan reduces the expression of hypoxia-induced marker, which is upregulated by PDT. (iii) PDT downregulates irinotecan-induced survivin expression to amplify the apoptotic and anti-proliferative effects. The clinical translation potential of the combination will also be highlighted.
Huang-Chiao Huang, Srivalleesha Mallidi, Joyce Liu, Chun-Te Chiang, Zhiming Mai, Ruth Goldschmidt, Imran Rizvi, Neema Ebrahim-Zadeh, and Tayyaba Hasan, "Mechanistic exploration of a bi-directional PDT-based combination in pancreatic cancer
(Conference Presentation)," Proc. SPIE 9694, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV, 96940W (Presented at SPIE BiOS: February 14, 2016; Published: 26 April 2016); https://doi.org/10.1117/12.2217925.4848635774001.
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