Exploring the TRAILs less travelled: TRAIL in cancer biology and therapy

Nat Rev Cancer. 2017 May 24;17(6):352-366. doi: 10.1038/nrc.2017.28.


The discovery that the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis of cancer cells without causing toxicity in mice has led to the in-depth study of pro-apoptotic TRAIL receptor (TRAIL-R) signalling and the development of biotherapeutic drug candidates that activate TRAIL-Rs. The outcome of clinical trials with these TRAIL-R agonists has, however, been disappointing so far. Recent evidence indicates that many cancers, in addition to being TRAIL resistant, use the endogenous TRAIL-TRAIL-R system to their own advantage. However, novel insight on two fronts - how resistance of cancer cells to TRAIL-based pro-apoptotic therapies might be overcome, and how the pro-tumorigenic effects of endogenous TRAIL might be countered - gives reasonable hope that the TRAIL system can be harnessed to treat cancer. In this Review we assess the status quo of our understanding of the biology of the TRAIL-TRAIL-R system - as well as the gaps therein - and discuss the opportunities and challenges in effectively targeting this pathway.

Publication types

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

MeSH terms

  • Humans
  • Neoplasms / etiology*
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / physiology*
  • Signal Transduction
  • TNF-Related Apoptosis-Inducing Ligand / physiology*


  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • TNF-Related Apoptosis-Inducing Ligand