Targeting the death receptor signaling pathway as a potential therapeutic target in the treatment of colorectal cancer

J Cell Physiol. 2018 Oct;233(10):6538-6549. doi: 10.1002/jcp.26640. Epub 2018 May 9.

Abstract

Despite advances in the diagnosis and treatment of colorectal cancer (CRC), it remains a major cause of cancer related death globally. There are currently no chemotherapeutic agents that have been found to eradicate the disease without adverse effects. A defect in the death receptor signaling pathway is a feature of CRC. The ligand of these receptors belongs to the tumor necrosis factor family, and that are particularly expressed by cells of the immune system, and that induce apoptosis in a caspase dependent manner. The fact that malignant cells are particularly sensitive to these ligands, compared to normal cells, has led to work on the assessment of compounds that activate this pathway in the treatment of CRC. Phase I trials have shown that these death receptor agonists are safe. Phase II and III trials are currently investigating the efficacy of these therapeutic agents in the treatment of CRC. In this review, we describe the biochemical death receptor signaling pathway and its relationship to CRC. We also summarize the current clinical studies that are targeting this signaling pathway in CRC treatment.

Keywords: colorectal cancer; death receptor signaling pathway; targeted therapy.

Publication types

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

MeSH terms

  • Apoptosis / drug effects
  • Cell Proliferation / drug effects*
  • Clinical Trials as Topic
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Humans
  • Receptors, Death Domain / antagonists & inhibitors
  • Receptors, Death Domain / genetics*
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Receptors, Death Domain
  • Tumor Necrosis Factor-alpha