Nanomedicine strategies to overcome the pathophysiological barriers of pancreatic cancer

A nearly impenetrable stroma and hypovascularity limit drug delivery to pancreatic ductal adenocarcinoma (PDAC) cells and thus the effectiveness of treatments, resulting in a very poor prognosis for patients Various nanoparticle-based approaches to overcome the biological barriers to drug delivery that are characteristic of pancreatic cancer are being explored in order to improve patient responses and outcomes Nanoformulations comprising albumin-bound paclitaxel (nab-paclitaxel) and liposomal irinotecan (MM-398) are approved for the treatment of PDAC based on survival benefits of 1.8–1.9 months Various signalling pathways (for instance, the MAPK/PI3K, Hedgehog, and autophagy cascades), and the KRAS oncogene are involved in the progression of pancreatic cancer and could serve as alternative therapeutic targets Strategies to overcome pathophysiological barriers and normalize the tumour matrix (such as Hedgehog-pathway inhibitors) can relieve the solid stress and improve vessel perfusion to increase nanoparticle penetration of the tumour Attributes of nanomedicine, such as small size, a high degree of drug encapsulation, and controlled drug release, can improve drug delivery to the tumour by exploiting novel endocytic routes that are independent of membrane transporters