A novel drug-delivery method that uses gemcitabine-laden poly(lactic-co-glycolic acid)-based microparticles (MPs) to treat pancreatic cancer is under investigation — and researchers running the experiment at Mount Sinai in New York, New York, were able to show that these encapsulations could promote cancer-cell-killing effects and modulate drug resistance in vitro and in vivo when compared with blank, unloaded MPs. The investigators presented their results during the 2018 AACR Pancreatic Cancer: Advances in Science and Clinical Care conference in Boston, Massachusetts.1
In previous studies, the investigators showed that when tested in 2 human pancreatic cell lines — PANC-1 and MIAPaCa-2 — both paclitaxel-loaded microparticles (PMPs) and gemcitabine-loaded microparticles (GMPs), either alone or in combination, were able to prompt the appearance of resistance biomarkers against the drugs.
In the current study, researchers were seeking to understand if treatment with the drug microparticles worked through the modulation of the MAPK stress pathway (p38 and JNK proteins).
They found that sequential treatment with the MPs (PMP followed by GMP) modulated the activation of phospho-p38 and phospho-JNK, which are active when there is oxidative stress inside a cell. This leads to activation of programmed cell death. Thus, the investigators determined that PMPs reduce resistance barriers and that, when combined with GMPs, PMPs are capable of enhancing cancer cell death.
Although follow-up studies are needed to confirm the efficacy of injecting PMPs in established mouse tumors, the researchers wrote that the “described drug delivery method has the potential to be a more efficient local treatment modality than systemic gemcitabine and paclitaxel against pancreatic cancer.”
- Munoz-Sagastibelza M, Soroka S, Martello-Rooney L, et al. Drug-loaded microparticles reduce gemcitabine resistance in pancreatic cancer. Presented at: AACR Pancreatic Cancer: Advances in Science and Clinical Care conference; Boston, Massachusetts: September 21-24, 2018. Abstract A041.