Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with five-year survival rates of 2-9% and is predicted to become the third leading cause of cancer death in the EU by 2025. PDAC tumors show hypovascularity and vascular compression, causing chemoresistance, resulting from desmoplasia by pancreatic stellate cells (PSCs). Evidence has shown that a pro-angiogenic approach for PDAC increases drug delivery and efficacy, reducing tumor growth and metastasis. Cold atmospheric plasma (CAP) treatment is a novel and safe technology known to induce angiogenesis at low treatment doses. The objective and novelty of my project is to use mild CAP treatment to enhance the delivery and effect of chemotherapeutic drugs by inducing angiogenesis for a synergistic anti-cancer effect. The kINPen® plasma jet will be used to determine optimal CAP treatment conditions. Spheroid co-cultures of pancreatic cancer cells, PSCs and endothelial cells will be investigated. Gemcitabine will be used as chemotherapeutic drug and administration to 3D spheroids will be performed with the novel OrganoPlate® Graft, which allows vascularization of 3D in vitro models and increases the predictive power of in vitro work. Clinical efficacy will be evaluated by combining distal pancreatectomy with intra-operative CAP treatment and adjuvant chemotherapy in an orthotopic mouse model. This project will lead to a novel combinational treatment strategy for PDAC patients that can have partial or full resection.
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