Pancreatic cancer, one of the most fatal types of human cancers, includes several non-epithelial and stromal components, such as activated fibroblasts, vascular cells, neural cells and immune cells, that are involved in different cancers. Vascular endothelial cell growth factor 165 receptors 1 [neuropilin-1 (NRP-1)] and 2 (NRP-2) play a role in the biological behaviors of pancreatic cancer and may appear as potential therapeutic targets. The NRP family of proteins serve as co-receptors for vascular endothelial growth factor, transforming growth factor β, hepatocyte growth factor, fibroblast growth factor, semaphorin 3, epidermal growth factor, insulin-like growth factor and platelet-derived growth factor. Investigations of mechanisms that involve the NRP family of proteins may help develop novel approaches for overcoming therapy resistance in pancreatic cancer. The present review aimed to provide an in-depth exploration of the multifaceted roles of the NRP family of proteins in pancreatic cancer, including recent findings from single-cell analysis conducted within the context of pancreatic adenocarcinoma, which revealed the intricate involvement of NRP proteins at the cellular level. Through these efforts, the present study endeavored to further reveal their relationships with different biological processes and their potential as therapeutic targets in various treatment modalities, offering novel perspectives and directions for the treatment of pancreatic cancer.

Semaphorins have been traditionally known as axon guidance proteins that negatively regulate axonal growth. However, in the past couple of decades, their versatile role in so many other biological processes has come to prominence as well. One such example is their role in cancer. In this review article, the focus was on the tumor proliferative and tumor suppressive role of all 20 semaphorin family members under the 7 semaphorin classes found in vertebrates and invertebrates as well as the ongoing and emerging therapeutic approaches to combat semaphorin-mediated cancers. Except sema6C, 19 of the 20 non-viral semaphorin family members have been discovered to be associated with cancer in one way or another. Eleven semaphorin family members have been discovered to be tumor proliferative and 8 to be tumor suppressive. Six therapeutic avenues and their safety profiles have been discussed which are currently at use or at the various stages of development. Finally, perspectives on which approach is the best for treating cancers associated with semaphorins have been given.