Abstract
Pancreatic cancer is a devastating disease with the worst outcome of any human cancer. Despite significant improvements in cancer treatment in general, little progress has been made in pancreatic cancer (PDAC), resulting in an overall 5-year survival rate of less than 10%. This dismal prognosis can be attributed to the limited clinical efficacy of systemic chemotherapy due to its high toxicity and consequent dose reductions. Targeted delivery of chemotherapeutic drugs to PDAC cells without affecting healthy non-tumor cells will largely reduce collateral toxicity leading to reduced morbidity and an increased number of PDAC patients eligible for chemotherapy treatment. To achieve targeted delivery in PDAC, several strategies have been explored over the last years, and especially the use of mesoporous silica nanoparticles (MSNs) seem an attractive approach. MSNs show high biocompatibility, are relatively easy to surface modify, and the porous structure of MSNs enables high drug-loading capacity. In the current systematic review, we explore the suitability of MSN-based targeted therapies in the setting of PDAC. We provide an extensive overview of MSN-formulations employed in preclinical PDAC models and conclude that MSN-based tumor-targeting strategies may indeed hold therapeutic potential for PDAC, although true clinical translation has lagged behind.
Highlights
Median survival rates of Pancreatic CancerPancreatic ductal adenocarcinoma (PDAC) are low at 11–15 months for resectable pancreatic cancer, 6–10 months for locally advanced cancer, and only 3–5 months for metastatic disease [5]
140 eligible papers were identified that were thoroughly screened for experimental data on mesoporous silica nanoparticles (MSNs) in PDAC
The preclinical studies discussed in this systematic review suggest that MSN-based tumor-targeting strategies may hold therapeutic potential for PDAC
Summary
Pancreatic ductal adenocarcinoma (PDAC), a neoplasm of the ductal cells in the exocrine pancreas, accounts for around 85% of pancreatic cancer diagnoses [1–3]. Median survival rates of PDAC are low at 11–15 months for resectable pancreatic cancer, 6–10 months for locally advanced cancer, and only 3–5 months for metastatic disease [5]. Treatment of PDAC depends on its disease stage and comprises surgical resection, radiation therapy, chemotherapy, and supportive care. Surgical resection is the only treatment with curative potential [7]. PDAC patients are divided into three groups; resectable/borderline resectable (10–20% of cases), non-resectable/locally advanced (around 30% of cases), and metastatic (around 60% of patients). Resectable/borderline resectable patients may receive neoadjuvant chemotherapy in combination with radiotherapy or adjuvant chemotherapy after surgical resection [8–10].
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