The Emerging Landscapes to Drug Delivery Systems for the Treatment of Pancreatic Cancer

Abstract

: Pancreatic Ductal Adenocarcinoma (PDA) is a highly metastatic tumor, and the liver is the first target, which restricts the use of medications. PDA is considered one of the most aggressive types of cancer in the world, with extremely short survival time, depending on the stage of diagnosis. In non-surgical cases, chemotherapy alternatives are only effective in 40% to 60% of patients. The low efficiency of treatments occurs mainly due to the complex microenvironment in PDA leading to chemoresistance to treatments and makes it difficult to access the drug. A very important histological characteristic of PDA is the extremely dense stroma, which leads to low vascularization of tumor tissue. Consequently, stroma environment causes less drug accumulation in tumor cells, even selective and/or targeted drugs. Overcoming the stroma's microenvironment is a major challenge for effective therapies that manage to get through this difficult access. Moreover, specific genes lead to direct chemoresistance of PDA, due to their high progression. In this scenario, nanotechnology appears as an alternative to overcome these clinical challenges that must be overcome concern two distinct ways: the stroma and the tumor properly. Thus, this review aimed to bring advances in the application of nanotechnology aiming to open up new landscapes against PDA. There are a huge number of nanoparticles carrying drugs in preclinical and clinical trials for the effective treatment of PDA. These works were discussed and it was proposed, based on the current scenario, the future prospects for an efficient treatment of PDA.

The Role of Neural Signaling in the Pancreatic Cancer Microenvironment

“…The tumor microenvironment of PDAC is characterized by its dense stroma with various cells such as fibroblasts, immune cells, blood vessels, and nerves [ 4 , 5 ]. These cells in the tumor microenvironment and tumor cells interact with each other to form a complex network and support tumor progression by providing nutrition [ 6 ], growth factors, and cytokines/chemokines [ 7 ], suppressing anti-tumor immunity [ 8 ], and inhibiting efficient drug delivery [ 9 ].…”

Nanoparticle-based delivery systems modulate the tumor microenvironment in pancreatic cancer for enhanced therapy

“…On the other hand, unlike other tumors, the tumor stroma of pancreatic cancer seems to act as a natural barrier between the body's immune system and the tumor, limiting the use of immunotherapy [ 16 , 17 ]. Most importantly, the barrier protects tumor cells from being attacked by conventional chemotherapy drugs to develop chemoresistance [ 18 ]. Therefore, when designing therapeutic strategies for pancreatic cancer, we have to consider the unique TME (Fig.…”