Broekgaarden, MansRizvi, ImranBulin, Anne-LaurePetrovic, LjubicaGoldschmidt, RuthMassodi, IqbalCelli, Jonathan P.Hasan, Tayyaba2018-04-192018Broekgaarden, Mans, Imran Rizvi, Anne-Laure Bulin, Ljubica Petrovic, Ruth Goldschmidt, Iqbal Massodi, Jonathan P. Celli, and Tayyaba Hasan. 2018. “Neoadjuvant photodynamic therapy augments immediate and prolonged oxaliplatin efficacy in metastatic pancreatic cancer organoids.” Oncotarget 9 (16): 13009-13022. doi:10.18632/oncotarget.24425. http://dx.doi.org/10.18632/oncotarget.24425.http://nrs.harvard.edu/urn-3:HUL.InstRepos:35982108Effective treatment of advanced metastatic disease remains the primary challenge in the management of inoperable pancreatic cancer. Current therapies such as oxaliplatin (OxPt)-based chemotherapy regimens (FOLFIRINOX) provide modest short-term survival improvements, yet with significant toxicity. Photodynamic therapy (PDT), a light-activated cancer therapy, demonstrated clinical promise for pancreatic cancer treatment and enhances conventional chemotherapies with non-overlapping toxicities. This study investigates the capacity of neoadjuvant PDT using a clinically-approved photosensitizer, benzoporphyrin derivative (BPD, verteporfin), to enhance OxPt efficacy in metastatic pancreatic cancer. Treatment effects were evaluated in organotypic three-dimensional (3D) cultures, clinically representative models that bridge the gap between conventional cell cultures and in vivo models. The temporally-spaced, multiparametric analyses demonstrated a superior efficacy for combined PDT+OxPt compared to each monotherapy alone, which was recapitulated on different organotypic pancreatic cancer cultures. The therapeutic benefit of neoadjuvant PDT to OxPt chemotherapy materialized in a time-dependent manner, reducing residual viable tissue and tumor viability in a manner not achievable with OxPt or PDT alone. These findings emphasize the need for intelligent combination therapies and relevant models to evaluate the temporal kinetics of interactions between mechanistically-distinct treatments and highlight the promise of PDT as a neoadjuvant treatment for disseminated pancreatic cancer.en-UStranslational therapiesorganoid modelsexperimental medicinecombination therapyphotochemotherapyJournal Article2018-04-1910.18632/oncotarget.24425