Disassembling a cancer puzzle: Cell junctions and plasma membrane as targets for anticancer therapy

J Control Release. 2018 Sep 28:286:125-136. doi: 10.1016/j.jconrel.2018.07.030. Epub 2018 Jul 17.

Abstract

Despite an enhanced permeability and retention effect typical of many solid tumors, drug penetration is not always sufficient. Possible strategies for the drug delivery improvement are a modification of the tumor cell-to-cell junctions and usage of cell membrane permeabilization proteins. In this review we discuss epithelial cell junctions as targets for a combined anticancer therapy and propose new possible sources of such agents. We suggest considering viral and bacterial pathogens disrupting epithelial layers as plentiful sources of new therapeutic agents for increasing tumor permeability for other effector agents. We also observe the application of pore forming proteins and peptides of different origin for cytoplasmic delivery of anti-cancer agents and consider the main obstacles of their use in vivo.

Keywords: Cancer; Cell junctions; Enhanced permeability; Junction opener; Pathogens; Pore-forming toxins.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Drug Delivery Systems / methods*
  • Humans
  • Intercellular Junctions / drug effects
  • Intercellular Junctions / metabolism*
  • Intercellular Junctions / pathology
  • Molecular Targeted Therapy / methods
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Permeability / drug effects

Substances

  • Antineoplastic Agents