Description

A prominent pathological feature of pancreatic cancer is the desmoplastic reaction. Desmoplasia is characterized by a dramatic rise in the proliferation of alpha-smooth muscle actin-positive fibroblasts as well as an increase in the deposition of numerous components of the extracellular matrix. The interstitial fluid pressure and overall tissue heterogeneity and elasticity are dramatically altered as a result of changes in stromal cell proliferation and the deposition of extracellular matrix components. It has been hypothesized that these modifications contribute to cancer chemoresistance. Desmoplasia-induced chemoresistance has both biological and physiological causes and effects. Desmoplasia in pancreatic cancer and how it might be contributing to resistance to current chemotherapeutic treatments are discussed in this chapter.

With a survival rate of less than 5%, Pancreatic Ductal Adeno Carcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. Chemoresistance to the preferred first-line treatment, gemcitabine, both intrinsic and acquired, is a factor in this poor prognosis. Chemoresistance in pancreatic cancer is caused by a number of different factors. Desmoplasia and the Tumor Micro Environment (TME) are becoming increasingly thought to be major contributors to PDAC's chemoresistance. The capacity of the "soil," or tumor microenvironment, to promote tumor cell growth has been increasingly recognized since Paget's seminal "seed" and "soil" hypothesis was proposed to reconcile measurable differences in the frequency of distal sites of metastasis. Numerous cellular and molecular components reside in the tumor microenvironment, also known as the stroma. In pancreatic cancer, the stroma's role in disease progression is still poorly understood, which is unfortunate. Desmoplasia, which is caused by the proliferation of alpha-smooth muscle actin-positive fibroblasts and the increased deposition of Extra Cellular Matrix (ECM) components, results in a decrease in the elasticity of the tumor tissue and an increase in the pressure of the tumor in the Interstitial Fluid (IFP). Reduced rate of therapeutic agent perfusion and, as a result, decreased efficacy are the consequences of increased IFP. In a variety of tumor types, it has been demonstrated that this physiological chemoresistance is a significant factor in the decreased efficacy of chemotherapeutics. Desmoplasia can also trigger a number of signaling cascades that make the body more resistant to therapeutic agents. As a result, agents that directly target the tumor cells and target elements of the tumor stroma that contribute to desmoplasia are gaining traction as a potential strategy for overcoming resistance and increasing efficacy. Desmoplasia and chemoresistance, as well as the possibility that desmoplasia is contributing to chemoresistance in pancreatic cancer.

A fundamental feature of PDAC is desmoplasia, which is also known as the desmoplastic reaction. Desmoplasia, which is derived from the Greek words desmos, which means "band" or "fastening," and plassein, which means "form" or "mold," has two known clinical manifestations a significant overproduction of proteins from the extracellular matrix and an extensive proliferation of cells that look like myofibroblasts. Therefore, both cellular and non-cellular components make up the dense and fibrous connective tissue results. Desmoplasia can have a variety of cellular components, including myofibroblast-like cells derived from stellate cells and infiltrating immune cells. Multiple Extra Cellular Matrix (ECM) proteins, including fibronectin, laminin, hyaluronan, and the glycoprotein osteonectin, have been identified as non-cellular components. Multiple intercellular and intracellular biological signaling events cause desmoplasia. Transforming Growth Factor (TGF), basic Fibroblast Growth Factor (FGF2), Connective Tissue Growth Factor (CTGF), and Inter Leukin-1 (IL-1) all appear to stimulate the production of ECM, according to reports. However, it has been demonstrated that the population of cells that resemble myofibroblasts is proliferated by platelet-derived growth factor (PDGF). Desmoplasia's cellular and non-cellular components both play a significant role in the development of pancreatic cancer.

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Jackson
Journal coordinator
Journal of Neoplasm