Positioning of Proteasome Inhibitors in Therapy of Solid Malignancies

Cancer Chemother Pharmacol. 2018 Feb;81(2):227-243. doi: 10.1007/s00280-017-3489-0. Epub 2017 Nov 28.

Abstract

Targeting of the protein degradation pathway, in particular, the ubiquitin-proteasome system, has emerged as an attractive novel cancer chemotherapeutic modality. Although proteasome inhibitors have been most successfully applied in the treatment of hematological malignancies, they also received continuing interest for the treatment of solid tumors. In this review, we summarize the current positioning of proteasome inhibitors in the treatment of common solid malignancies (e.g., lung, colon, pancreas, breast, and head and neck cancer), addressing topics of their mechanism(s) of action, predictive factors and molecular mechanisms of resistance.

Keywords: Bortezomib; Carfilzomib; Drug resistance; Proteasome inhibitors; Solid tumors.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Drug Resistance, Neoplasm
  • Humans
  • Neoplasms / drug therapy*
  • Proteasome Endopeptidase Complex / chemistry
  • Proteasome Endopeptidase Complex / drug effects
  • Proteasome Inhibitors / pharmacology*
  • Proteasome Inhibitors / therapeutic use*

Substances

  • Antineoplastic Agents
  • Proteasome Inhibitors
  • Proteasome Endopeptidase Complex