Pancreatic cancer is a devastating disease with a dismal prognosis. It is the fourth leading cause of cancer-related deaths in western societies, with a 5-year survival rate of less than 5%. Current treatments for pancreatic cancer have limited efficacy. Therefore, it is clear that alternative approaches are needed to improve the outcome of this condition. A key histopathological feature of pancreatic cancer which is associated with its innate clinical and biological aggressiveness is its pronounced desmoplastic (stromal) reaction, which is now considered an alternative therapeutic target in pancreatic cancer. Stroma production is stimulated by cancer-cell derived growth factors. The desmoplastic reaction is composed of extracellular matrix (ECM) proteins, primarily type I and III collagen, fibronectin and proteoglycans; small endothelium lined vessels; and a diverse population of cells including inflammatory cells, fibroblasts and stellate cells.
Stromal cells are altered by cytokines and growth factors secreted by tumor cells. Reciprocally, the stromal cells promote tumor cell migration, growth, invasion and resistance to drugs and apoptosis. Pancreatic stellate cells (PSCs) have recently emerged as the principal regulator of the desmoplastic reaction in pancreatic cancer, as well as key effector cells in pancreatic fibrosis during necroinflammation in chronic pancreatitis a known risk factor for pancreatic cancer. Furthermore, the extensive ECM deposition by PSCs in pancreatic cancer causes distortion and compression of tumor vasculature by fibrous tissue which contributes to tumor hypoxia, a determinant of chemoresistance. An improved knowledge of PSC biology has the potential to provide an insight into pathways that may be therapeutically targeted to inhibit PSC activation, thereby inhibiting the development of fibrosis in pancreatic cancer and interrupting stellate cell - cancer cell interactions so as to retard cancer progression.
The goal of this Research Topic is to review the advancements in our understanding of the tumor-stromal interactions and how this contributes to pancreatic cancer progression. It is an opportunity for experts in this field to submit a viewpoint, commentary, research letter, research article, review or methodologies in a cutting edge area of research and a way for us to communicate research priorities to maximize the chances of improving the treatment of patients with pancreatic cancer.
Pancreatic cancer is a devastating disease with a dismal prognosis. It is the fourth leading cause of cancer-related deaths in western societies, with a 5-year survival rate of less than 5%. Current treatments for pancreatic cancer have limited efficacy. Therefore, it is clear that alternative approaches are needed to improve the outcome of this condition. A key histopathological feature of pancreatic cancer which is associated with its innate clinical and biological aggressiveness is its pronounced desmoplastic (stromal) reaction, which is now considered an alternative therapeutic target in pancreatic cancer. Stroma production is stimulated by cancer-cell derived growth factors. The desmoplastic reaction is composed of extracellular matrix (ECM) proteins, primarily type I and III collagen, fibronectin and proteoglycans; small endothelium lined vessels; and a diverse population of cells including inflammatory cells, fibroblasts and stellate cells.
Stromal cells are altered by cytokines and growth factors secreted by tumor cells. Reciprocally, the stromal cells promote tumor cell migration, growth, invasion and resistance to drugs and apoptosis. Pancreatic stellate cells (PSCs) have recently emerged as the principal regulator of the desmoplastic reaction in pancreatic cancer, as well as key effector cells in pancreatic fibrosis during necroinflammation in chronic pancreatitis a known risk factor for pancreatic cancer. Furthermore, the extensive ECM deposition by PSCs in pancreatic cancer causes distortion and compression of tumor vasculature by fibrous tissue which contributes to tumor hypoxia, a determinant of chemoresistance. An improved knowledge of PSC biology has the potential to provide an insight into pathways that may be therapeutically targeted to inhibit PSC activation, thereby inhibiting the development of fibrosis in pancreatic cancer and interrupting stellate cell - cancer cell interactions so as to retard cancer progression.
The goal of this Research Topic is to review the advancements in our understanding of the tumor-stromal interactions and how this contributes to pancreatic cancer progression. It is an opportunity for experts in this field to submit a viewpoint, commentary, research letter, research article, review or methodologies in a cutting edge area of research and a way for us to communicate research priorities to maximize the chances of improving the treatment of patients with pancreatic cancer.