The Stress Kinase p38α as a Target for Cancer Therapy

Cancer Res. 2015 Oct 1;75(19):3997-4002. doi: 10.1158/0008-5472.CAN-15-0173. Epub 2015 Sep 16.

Abstract

p38α is a ubiquitous protein kinase strongly activated by stress signals, inflammatory cytokines, and many other stimuli, which has been implicated in the modulation of multiple cellular processes. There is good evidence in the literature that p38α plays an important tumor-suppressor role by interfering with malignant cell transformation. This is mainly based on the ability of the p38α pathway to regulate tissue homeostasis by integrating signals that balance cell proliferation and differentiation or induce apoptosis. However, recent reports have also illustrated protumorigenic functions for p38α. Thus, p38α signaling may facilitate the survival and proliferation of tumor cells contributing to the progression of some tumor types. In addition, p38α activation helps tumor cells to survive chemotherapeutic treatments. In all these cases, the inhibition of p38α has a potential therapeutic interest. Further elucidation of the context-dependent functions of p38α signaling in tumoral processes is of obvious importance for the use of inhibitors of this pathway in cancer therapy.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Cell Transformation, Neoplastic / drug effects
  • Colon / enzymology
  • Drug Synergism
  • Enzyme Activation / drug effects
  • Humans
  • Liver / enzymology
  • Lung / enzymology
  • Mice
  • Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 14 / physiology
  • Molecular Targeted Therapy*
  • Neoplasm Metastasis
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / physiology
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / enzymology
  • Phosphorylation / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein Processing, Post-Translational / drug effects
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Tumor Microenvironment / drug effects

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins
  • Protein Kinase Inhibitors
  • Mitogen-Activated Protein Kinase 14