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The three Rs along the TRAIL: resistance, re-sensitization and reactive oxygen species (ROS)

Gregory Mellier1, Shazib Pervaiz

  • 1Department of Physiology, Yong Loo Lin School of Medicine, Singapore.

Free Radical Research
|May 8, 2012
PubMed

Insights

Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) can trigger cancer cell death. However, cancer cells can become resistant to TRAIL, but small molecules and reactive oxygen species may help overcome this resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) pathway induces apoptosis in cancer cells.
  • TRAIL-based cancer therapies show promise but face challenges due to resistance.
  • Understanding TRAIL resistance mechanisms is crucial for developing effective cancer treatments.

Purpose of the Study:

  • To review the biology of TRAIL signaling in cancer.
  • To highlight mechanisms of TRAIL resistance in cancer cells.
  • To explore small molecule compounds and reactive oxygen species in overcoming TRAIL resistance.

Main Methods:

  • Literature review of TRAIL signaling and resistance mechanisms.
  • Analysis of studies investigating small molecule compounds for TRAIL sensitization.
  • Examination of the role of intracellular reactive oxygen species (ROS) in TRAIL response.

Main Results:

  • TRAIL receptor ligation triggers cancer-specific apoptosis in various models.
  • Cancer cells can develop resistance to TRAIL-mediated apoptosis.
  • Small molecule compounds can re-sensitize cancer cells to TRAIL.
  • Intracellular reactive oxygen species (ROS) play a critical role in regulating cancer cell response to TRAIL.

Conclusions:

  • TRAIL is a promising cancer therapeutic, but resistance is a significant hurdle.
  • Small molecules and modulation of reactive oxygen species (ROS) are potential strategies to enhance TRAIL efficacy.
  • Targeting intracellular ROS may be a key approach to overcome TRAIL resistance in cancer therapy.

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