Leader: Buddhadev Layek, PhD
Project Title: Mesenchymal Stem Cell-Based Targeted Combined Therapy for Pancreatic Ductal Adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies, with a five-year survival rate of 10.8%. The complexity of pancreatic cancer growth and progression has largely overwhelmed the best clinical efforts to date. The lack of efficient strategies to achieve cytotoxic concentrations of chemotherapeutics in the tumor tissue and the tumor’s innate resistance to chemotherapy are the significant barriers to improving treatment outcomes for PDAC. Thus, new approaches for tumor-selective delivery of chemotherapeutics can enhance the therapeutic efficacy while minimizing chemotherapy-associated toxicities.
Our research will evaluate a new approach for treating PDAC with a combination of a novel histone deacetylase (HDAC) inhibitor, entinostat, and a leading chemotherapeutic agent, oxaliplatin, at their synergistic ratio. In this project, we will use nanoparticle-loaded MSCs (nano-MSCs) as a drug delivery platform to selectively accumulate cytotoxic agents in pancreatic tumors. Based on the existing literature and our preliminary findings, we hypothesize that MSCs-mediated tumor-targeted delivery of oxaliplatin and entinostat at their synergistic ratio would significantly reduce pancreatic tumor growth and enhance the efficacy without acute toxicity. Further, this research will aim to delineate the underlined mechanisms of action and therapeutic efficacy of entinostat and oxaliplatin combination for PDAC.