Adapting and Surviving: Intra and Extra-Cellular Remodeling in Drug-Resistant Gastric Cancer Cells

Int J Mol Sci. 2019 Jul 31;20(15):3736. doi: 10.3390/ijms20153736.

Abstract

Despite the significant recent advances in clinical practice, gastric cancer (GC) represents a leading cause of cancer-related deaths in the world. In fact, occurrence of chemo-resistance still remains a daunting hindrance to effectiveness of the current approach to GC therapy. There is accumulating evidence that a plethora of cellular and molecular factors is implicated in drug-induced phenotypical switching of GC cells. Among them, epithelial-mesenchymal transition (EMT), autophagy, drug detoxification, DNA damage response and drug target alterations, have been reported as major determinants. Intriguingly, resistant GC phenotype may be the result of GC cell-induced tumor microenvironment (TME) remodeling, which is currently emerging as a key player in promoting drug resistance and overcoming cytotoxic effects of drugs. In this review, we discuss the possible mechanisms of drug resistance and their involvement in determining current GC therapies failure.

Keywords: cell behavior; cellular reprogramming; drug resistance; gastric cancer.

Publication types

  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Antineoplastic Agents / therapeutic use
  • Autophagy / drug effects
  • Autophagy / genetics*
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism
  • Cell Survival / genetics
  • Drug Resistance, Neoplasm / genetics*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic*
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / genetics
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / pathology
  • Helicobacter pylori / growth & development
  • Helicobacter pylori / pathogenicity
  • Humans
  • Hypoxia / drug therapy
  • Hypoxia / genetics
  • Hypoxia / metabolism
  • Hypoxia / pathology
  • Inactivation, Metabolic / genetics
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics*

Substances

  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • Autophagy-Related Proteins
  • MicroRNAs
  • Neoplasm Proteins