TRAIL of Hope Meeting Resistance in Cancer

Trends Cancer. 2020 Dec;6(12):989-1001. doi: 10.1016/j.trecan.2020.06.006. Epub 2020 Jul 24.

Abstract

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis selectively via its interaction with the death receptors TRAILR1/DR4 and TRAILR2/DR5 in a wide range of cancers, while sparing normal cells. Despite its tremendous potential for cancer therapeutics, the translation of TRAIL into the clinic has been confounded by TRAIL-resistant cancer populations. We discuss different molecular mechanisms underlying TRAIL-mediated apoptosis and resistance to TRAIL. We also discuss the successes and failures of recent preclinical and clinical studies of TRAIL-induced apoptosis, and current attempts to overcome TRAIL resistance, and we provide a perspective for improving the prospects of future clinical implementation.

Keywords: TRAIL; apoptosis; cancer; therapeutic resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • Chemoradiotherapy / methods
  • Clinical Trials as Topic
  • DNA Damage / drug effects
  • DNA Damage / radiation effects
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Drug Resistance, Neoplasm / radiation effects
  • Drug Screening Assays, Antitumor
  • Epigenesis, Genetic / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Half-Life
  • Humans
  • Immunotherapy / methods
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*
  • TNF-Related Apoptosis-Inducing Ligand / therapeutic use
  • Treatment Outcome
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / radiation effects

Substances

  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10A protein, human
  • TNFRSF10B protein, human
  • TNFSF10 protein, human