Abstract
Despite recent advancements, effective treatment for pancreatic ductal adenocarcinoma (PDAC) has remained elusive. The overall survival rate in PDAC patients has been dismally low due to resistance to standard therapies. In fact, the failure of monotherapies to provide long-term survival benefits in patients led to ascension of several combination therapies for PDAC treatment. However, these combination therapies provided modest survival improvements while increasing treatment-related adverse side effects. Hence, recent developments in drug delivery methods hold the potential for enhancing therapeutic benefits by offering cocktail drug loading and minimizing chemotherapy-associated side effects. Nanoformulations-aided deliveries of anticancer agents have been a success in recent years. Yet, improving the tumor-targeted delivery of drugs to PDAC remains a major hurdle. In the present paper, we developed several new tumor-targeted dual intervention-oriented drug-encapsulated (DIODE) liposomes. We successfully formulated liposomes loaded with gemcitabine (G), paclitaxel (P), erlotinib (E), XL-184 (c-Met inhibitor, X), and their combinations (GP, GE, and GX) and evaluated their in vitro and in vivo efficacies. Our novel DIODE liposomal formulations improved median survival in comparison with gemcitabine-loaded liposomes or vehicle. Our findings are suggestive of the importance of the targeted delivery for combination therapies in improving pancreatic cancer treatment.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, having a 5-year survival rate of less than 8% [1]
A prior report showed that first-line treatment with erlotinib/gemcitabine was comparable to FOLFIRINOX in achieving a 1-year survival rate in rash-positive metastatic PDAC patients [16]
The hydrodynamic diameters and zeta potentials of both empty and drug-loaded liposomal formulations were measured by using the dynamic light scattering (DLS) technique
Summary
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, having a 5-year survival rate of less than 8% [1]. The reasons behind such poor prognosis have been postulated due to late-stage diagnosis and resistance to standard therapies [2,3,4]. Combination treatment options help in improving the therapeutic benefit by sensitizing tumors toward anticancer drugs [11,12]. Nab-paclitaxel (PTX) combined with gemcitabine demonstrates a better median overall survival rate than gemcitabine alone [13,14,15]. The overall survival of Cancers 2020, 12, 1189; doi:10.3390/cancers12051189 www.mdpi.com/journal/cancers
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