Management of Pancreatic Cancer and Its Microenvironment: Potential Impact of Nano-Targeting

SIMPLE SUMMARY: The poor prognosis and survival rates associated with pancreatic cancer show that there is a clear unmet need for better disease management. The heterogeneity of the tumor and its microenvironment, including stroma and fibrosis, creates a challenge for current therapy. The pathogenesis of pancreatic cancer is mediated by several factors, such as severed communication between pancreatic stellate cells and stroma and the consequences of hypoxia-inducible factors that aid in the survival of the pancreatic tumor. Given the multiple limitations of molecular targeting, multiple functional nano-targeting offers a breakthrough in pancreatic cancer treatment through its ability to overcome the physical challenges posed by the tumor microenvironment, amongst many others. ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is rare and difficult to treat, making it a complicated diagnosis for every patient. These patients have a low survival rate along with a poor quality of life under current pancreatic cancer therapies that adversely affect healthy cells due to the lack of precise drug targeting. Additionally, chemoresistance and radioresistance are other key challenges in PDAC, which might be due in part to the lack of tumor-targeted delivery of sufficient levels of different chemotherapies because of their low therapeutic index. Thus, instead of leaving a trail of off-target damage when killing these cancer cells, it is best to find a way that targets them directly. More seriously, metastatic relapse often occurs after surgery, and therefore, achieving improved outcomes in the management of PDAC in the absence of strategies preventing metastasis is likely to be impossible. Nano-targeting of the tumor and its microenvironment has shown promise for treating various cancers, which might be a promising approach for PDAC. This review updates the advancements in treatment modalities for pancreatic cancer and highlights future directions that warrant further investigation to increase pancreatic patients’ overall survival.