Drug resistance to conventional therapies remains a major cause of treatment failure, tumor recurrence and dismal survival rates for patients with advanced stage cancers. Photodynamic therapy (PDT) provides an opportunity to exploit photochemically-triggered death mechanisms via targeting of sub-cellular, cellular and stromal compartments to overcome treatment resistance in unresponsive populations of stubborn disease. The informed design of mechanism-based combinations is emerging as increasingly important to targeting resistance and improving the efficacy of conventional treatments, while minimizing toxicity. PDT has been shown to synergize with conventional agents and to overcome the evasion pathways that cause resistance. Increasing evidence shows that PDT-based combinations cooperate mechanistically with, and improve the therapeutic index of, traditional chemotherapies. These and other findings emphasize the importance of including PDT as part of comprehensive treatment plans for cancer, particularly in complex disease sites. Identifying effective combinations requires a multi-faceted approach that includes the development of bioengineered cancer models and corresponding image analysis tools. The presentation will focus on the molecular and phenotypic basis of verteporfin PDT-based enhancement of chemotherapeutic efficacy and predictability in complex 3D models and in vivo models, with a particular emphasis on ovarian and pancreatic cancer.
Imran Rizvi, Shubhankar Nath, Girgis Obaid, Huang-Chiao Huang, Mans Broekgaarden, Anne-Laure Bulin, Sriram R. Anbil, Utkan Demirci, David H. Kessel, and Tayyaba Hasan, "Photodynamic therapy-based combinations to overcome molecular, cellular and stromal resistance mechanisms in ovarian and pancreatic cancer (Conference Presentation)," Proc. SPIE 10476, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVII, 1047604 (Presented at SPIE BiOS: January 27, 2018; Published: 14 March 2018); https://doi.org/10.1117/12.2290472.5751470630001.
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