Pancreatic Adenocarcinoma Invasiveness and the Tumor Microenvironment: From Biology to Clinical Trials

Abstract

Pancreatic adenocarcinoma (PDAC) originates in the glandular compartment of the exocrine pancreas. Histologically, PDAC tumors are characterized by a parenchyma that is embedded in a particularly prominent stromal component or desmoplastic stroma. The unique characteristics of the desmoplastic stroma shape the microenvironment of PDAC and modulate the reciprocal interactions between cancer and stromal cells in ways that have profound effects in the pathophysiology and treatment of this disease. Here, we review some of the most recent findings regarding the regulation of PDAC cell invasion by the unique microenvironment of this tumor, and how new knowledge is being translated into novel therapeutic approaches.

Cellular metabolism in pancreatic cancer as a tool for prognosis and treatment (Review)

“…Notably, using the algorithmic separation of tumor, stromal and normal gene expression, they also identified distinct stromal subtypes, which were defined as 'normal' and 'activated' and were independently prognostic. These findings demonstrate a particular significance of the stromal compartment, which has been shown to play crucial roles in PDAC biology (30)(31)(32)(33)(34)(35). It is also becoming clear that further heterogeneity in expression profiles exists within cells of a single tumor (36).…”

Molecular Changes Underlying Hypertrophic Scarring Following Burns Involve Specific Deregulations at All Wound Healing Stages (Inflammation, Proliferation and Maturation)

“…Failure of the maturation and modeling phase may result in excessive collagen accumulation and formation of hypertrophic scars with enormous rigidity ( Figure 6 ), or even in formation of a specific, not easily treatable unit—keloid. The connective tissue of keloid is morphologically similar to desmoplastic stroma of some tumors, especially of pancreatic adenocarcinoma [ 175 ]. In this context, fibroblasts isolated from keloids are very similar to cancer-associated fibroblasts isolated from the tumor stroma not only by expression of α-SMA, but also by expression of transcripts encoding inflammation-supporting cytokines and/or chemokines [ 176 ].…”

Noncoding RNAs Associated with Therapeutic Resistance in Pancreatic Cancer

“…Most pancreatic cancer (PaC) patients are diagnosed at an advanced stage owing to the lack of early detections; therefore, surgical management is unavailable for over 80% of patients [ 1 , 2 ]. Moreover, PaC is resistant to treatment options, such as radiotherapy, chemotherapy, and targeted therapy [ 1 , 3 , 4 ]. These features underline the requirement of developing more effective treatments for PaC.…”