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TRAIL and cancer therapy

Frank A E Kruyt1

  • 1Department of Medical Oncology, VU University Medical Center, CCA-Building, Room 2.36, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands. kruyt@vumc.nl

Cancer Letters
|March 11, 2008
PubMed

Insights

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy shows promise for cancer treatment but faces resistance. Combining TRAIL with specific agents targeting apoptotic blockades or survival signals can overcome resistance and improve outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • TRAIL receptors are key targets for selective cancer cell elimination.
  • TRAIL-based therapies (proteins, antibodies) demonstrate antitumor activity with few side effects.
  • Resistance to TRAIL therapy necessitates combination treatments with sensitizing agents.

Purpose of the Study:

  • To provide an overview of the TRAIL signaling pathway.
  • To summarize early clinical results of TRAIL therapy.
  • To highlight mechanisms of TRAIL resistance and strategies to overcome them.

Main Methods:

  • Review of TRAIL signaling pathway.
  • Analysis of clinical trial data for TRAIL therapy.
  • Discussion of targeted agents to overcome TRAIL resistance.

Main Results:

  • TRAIL therapy shows encouraging antitumor effects but frequently encounters resistance.
  • Standard chemotherapeutics can enhance TRAIL sensitivity.
  • Targeted agents neutralizing apoptotic blockades or suppressing prosurvival signals are effective.

Conclusions:

  • TRAIL therapy is a promising cancer treatment strategy.
  • Overcoming TRAIL resistance is crucial for maximizing therapeutic potential.
  • Targeted agents, including inhibitors of IAPs, Bcl-2 family, HDACi, and modulators of NF-kappaB, Raf, and EGFR, offer effective strategies to enhance TRAIL efficacy.

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