Mechanisms of drug resistance of pancreatic ductal adenocarcinoma at different levels

Biosci Rep. 2020 Jul 31;40(7):BSR20200401. doi: 10.1042/BSR20200401.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death worldwide, and the mortality of patients with PDAC has not significantly decreased over the last few decades. Novel strategies exhibiting promising effects in preclinical or phase I/II clinical trials are often situated in an embarrassing condition owing to the disappointing results in phase III trials. The efficacy of the current therapeutic regimens is consistently compromised by the mechanisms of drug resistance at different levels, distinctly more intractable than several other solid tumours. In this review, the main mechanisms of drug resistance clinicians and investigators are dealing with during the exploitation and exploration of the anti-tumour effects of drugs in PDAC treatment are summarized. Corresponding measures to overcome these limitations are also discussed.

Keywords: Cellular immunotherapies; Drug resistance; Gemcitabine; Molecular targeted therapy; Pancreatic ductal adenocarcinoma (PDAC).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics
  • Carcinoma, Pancreatic Ductal / blood supply
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / mortality
  • Cell Hypoxia
  • Clinical Trials as Topic
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Deoxycytidine / therapeutic use
  • Drug Resistance, Neoplasm*
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Gemcitabine
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Irinotecan / pharmacology
  • Irinotecan / therapeutic use
  • Leucovorin / pharmacology
  • Leucovorin / therapeutic use
  • Molecular Targeted Therapy / adverse effects
  • Molecular Targeted Therapy / methods
  • Mutation
  • Oxaliplatin / pharmacology
  • Oxaliplatin / therapeutic use
  • Pancreas / blood supply
  • Pancreas / drug effects
  • Pancreas / pathology
  • Pancreatic Neoplasms / blood supply
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / mortality
  • Progression-Free Survival
  • Survival Rate
  • Treatment Outcome
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics

Substances

  • Biomarkers, Tumor
  • folfirinox
  • Oxaliplatin
  • Deoxycytidine
  • Irinotecan
  • Leucovorin
  • Fluorouracil
  • Gemcitabine