The Roles of Frequently Mutated Genes of Pancreatic Cancer in Regulation of Tumor Microenvironment

Technol Cancer Res Treat. 2020 Jan-Dec:19:1533033820920969. doi: 10.1177/1533033820920969.

Abstract

Pancreatic ductal adenocarcinoma has extremely high malignancy and patients with pancreatic ductal adenocarcinoma have dismal prognosis. The failure of pancreatic ductal adenocarcinoma treatment is largely due to the tumor microenvironment, which is featured by ample stromal cells and complicated extracellular matrix. Recent genomic analysis revealed that pancreatic ductal adenocarcinoma harbors frequently mutated genes including KRAS, TP53, CDKN2A, and SMAD4, which can widely alter cellular processes and behaviors. As shown by accumulating studies, these mutant genes may also change tumor microenvironment, which in turn affects pancreatic ductal adenocarcinoma progression. In this review, we summarize the role of such genetic mutations in tumor microenvironment regulation and potential mechanisms.

Keywords: genetic mutation; local immunity; pancreatic ductal adenocarcinoma; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / immunology
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Humans
  • Mutation*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Smad4 Protein / genetics
  • Tumor Microenvironment / genetics*
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • KRAS protein, human
  • SMAD4 protein, human
  • Smad4 Protein
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins p21(ras)