Nanovector-based therapies in advanced pancreatic cancer

Abstract

Systemic therapy for advanced pancreatic cancer has been largely disappointing owing to the unfavorable pharmacokinetic profile and poor penetration of current chemotherapeutic agents ,as well as the fragile patient population with compromised tolerance to toxic chemotherapies. Nanovectors can provide passive drug delivery through abnormal tumor neo-vasculature microanatomy or active targeting via binding to receptors or macromolecules associated with the tumor. In such a manner, nanovector-based therapy may not only modulate the pharmacokinetics and therapeutic index of chemotherapeutic agents but also provide new treatment options in patients with advanced pancreatic cancer. In this article, we present the rationale and currently available clinical results of nanovector-based therapies to highlight the potential use of this class of agent in patients with advanced pancreatic cancer.

Keywords: CPT-11; EndoTAG-1; PEP02; liposome; nab-paclitaxel; nanoplatin; nanovector; pancreatic cancer; platinum.

Conflict of interest statement

No potential conflict of interest.

Figures

Figure 1. Nude mice were orthotopically implanted with COLO357/L3.6pI-T xenografts into the pancreas. Following ip administration of luciferin, animals were immediately imaged using a Xenogen IVIS 100 bioluminescence system, and subsequently imaged at weekly intervals. The signal was quantified by defining regions of interest (ROIs) and measuring photons/sec/str. Quantitative BLI values at post implantation day 7 were used to assign mice to treatment groups of five mice per group. Treatments included nanoliposomal CPT-11 at 20 mg/kg, free CPT-11 at 20 mg/kg or vehicle control. All treatments were administered i.v. by tail vein injection beginning at 7 days post- tumor implantation and continued weekly for a total of 3 planned treatments. (A) Bioluminescence images of nude mice on weeks 1-7. (B) BLI values over time. Free CPT-11 treatment (diamonds) produced partial inhibition of tumor growth at initial time points, followed by rapid growth approaching that of the vehicle control group (+). Nanoliposomal CPT-11 treatment (circles) produced complete inhibition of tumor growth at all time points.