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Is TRAIL the holy grail of cancer therapy?

Thomas Newsom-Davis1, Silvia Prieske, Henning Walczak

  • 1Department of Immunology, Tumour Immunology Unit, Imperial College London, Hammersmith Campus, London, UK.

Apoptosis : an International Journal on Programmed Cell Death
|February 6, 2009
PubMed

Insights

Tumour necrosis factor apoptosis inducing ligand (TRAIL) therapies show promise for cancer treatment by selectively inducing cancer cell death. However, resistance necessitates combination strategies to enhance TRAIL

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Apoptosis induction is a key strategy in anti-cancer drug development.
  • Tumour necrosis factor apoptosis inducing ligand (TRAIL) therapies selectively target cancer cells for apoptosis.
  • Many primary tumors exhibit resistance to TRAIL-mediated apoptosis, limiting its efficacy.

Purpose of the Study:

  • To review the mechanisms of TRAIL signaling, including both apoptotic and non-apoptotic pathways.
  • To evaluate the therapeutic potential of TRAIL-based treatments.
  • To explore the role of sensitizing agents in overcoming TRAIL resistance.

Main Methods:

  • Literature review of studies on TRAIL signaling pathways.
  • Analysis of preclinical and clinical data on TRAIL-based monotherapy.
  • Examination of combination therapies involving TRAIL and sensitizing agents.

Main Results:

  • TRAIL triggers apoptosis through death receptors but also activates non-apoptotic pathways.
  • TRAIL monotherapy shows efficacy in sensitive tumors but faces resistance in others.
  • Combination therapies with sensitizing agents can enhance TRAIL-induced apoptosis in resistant tumors.

Conclusions:

  • Understanding TRAIL signaling is crucial for optimizing cancer therapy.
  • TRAIL-based treatments, particularly in combination, offer a promising strategy against resistant cancers.
  • Further research into sensitizing agents is needed to broaden the application of TRAIL therapy.

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