Immune-Based Therapies and the Role of Microsatellite Instability in Pancreatic Cancer

Genes (Basel). 2020 Dec 29;12(1):33. doi: 10.3390/genes12010033.

Abstract

Pancreatic cancer is one of the most aggressive malignancies with limited treatment options thus resulting in high morbidity and mortality. Among all cancers, with a five-year survival rates of only 2-9%, pancreatic cancer holds the worst prognostic outcome for patients. To improve the overall survival, an earlier diagnosis and stratification of cancer patients for personalized treatment options are urgent needs. A minority of pancreatic cancers belong to the spectrum of Lynch syndrome-associated cancers and are characterized by microsatellite instability (MSI). MSI is a consequence of defective mismatch repair protein functions and it has been well characterized in other gastrointestinal tumors such as colorectal and gastric cancer. In the latter, high levels of MSI are linked to a better prognosis and to an increased benefit to immune-based therapies. Therefore, the same therapies could offer an opportunity of treatment for pancreatic cancer patients with MSI. In this review, we summarize the current knowledge about immune-based therapies and MSI in pancreatic cancer.

Keywords: Lynch syndrome; immune-based therapy; microsatellite instability; mismatch repair system; pancreatic cancer.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cancer Vaccines / therapeutic use
  • Chemotherapy, Adjuvant / methods
  • Clinical Trials as Topic
  • Colorectal Neoplasms, Hereditary Nonpolyposis / complications*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / immunology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / therapy
  • Disease-Free Survival
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy / methods*
  • Microsatellite Instability*
  • Mutation
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / prevention & control
  • Pancreatectomy
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / therapy*
  • Patient Selection
  • Precision Medicine / methods
  • Prognosis
  • Survival Rate

Substances

  • Cancer Vaccines
  • Immune Checkpoint Inhibitors