Pancreatic Cancer-Secreted Proteins: Targeting Their Functions in Tumor Microenvironment

Abstract

Pancreatic Ductal Adenocarcinoma (PDAC) is a ravaging disease with a poor prognosis, requiring a more detailed understanding of its biology to foster the development of effective therapies. The unsatisfactory results of treatments targeting cell proliferation and its related mechanisms suggest a shift in focus towards the inflammatory tumor microenvironment (TME). Here, we discuss the role of cancer-secreted proteins in the complex TME tumor-stroma crosstalk, shedding lights on druggable molecular targets for the development of innovative, safer and more efficient therapeutic strategies.

Keywords: cell signaling; monoclonal antibodies; pancreatic ductal adenocarcinoma; secretome; small molecules; tumor microenvironment.

Figure 1

Proteins Functions—A Global Core Biodata Resource, Panther Classification System (https://pantherdb.org/, accessed on 11 June 2023), classified the gene dataset for functions. Proteins secreted by pancreatic cancer cells were classified as having a general function (left column) or a specific function (right column). An Alluvial plot (https://www.mapequation.org/alluvial/, accessed on 28 June 2023) was used to depict the classifications. Furthermore, percentages of secreted proteins having common general functions are reported in the left column. A color code was used for each general function. In the column, the most represented protein functions are in the plot’s lower part.

Figure 2

Druggable secreted proteins landscape in pancreatic cancer cells. Inhibition arrows were used for small molecule drugs. Image was realized using Biorender (https://app.biorender.com/, accessed on 7 June 2023).