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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
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The therapeutic potential of TRAIL receptor signalling in cancer cells

R Yerbes1, C Palacios, A López-Rivas

  • 1Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas, Sevilla, Spain.

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
|December 1, 2011
PubMed

Insights

Tumor necrosis-related apoptosis-inducing ligand (TRAIL) shows promise for cancer therapy by selectively inducing cancer cell death. Clinical trials suggest TRAIL receptor agonists are effective with manageable toxicity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Activation of apoptotic pathways via death receptor ligands is a potential cancer treatment.
  • Tumor necrosis factor-alpha (TNF-α) and CD95 ligand treatments can cause severe toxicity.
  • Tumor necrosis-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells while sparing most normal cells.

Purpose of the Study:

  • To review the current understanding of TRAIL signaling pathways (both apoptotic and non-apoptotic).
  • To evaluate the therapeutic potential of TRAIL-based strategies in cancer treatment.
  • To summarize findings from Phase 1 and 2 clinical trials involving TRAIL or TRAIL receptor agonists.

Main Methods:

  • Review of existing literature on TRAIL signaling and its preclinical/clinical applications.
  • Analysis of data from preclinical studies in mice and nonhuman primates.
  • Examination of results from Phase 1 and 2 clinical trials of TRAIL-based therapies.

Main Results:

  • TRAIL effectively induces apoptosis in various cancer cells without significant systemic toxicity in preclinical models.
  • TRAIL receptor agonists demonstrated tumor growth suppression in xenograft models.
  • Clinical trials indicate efficacy of TRAIL or TRAIL receptor agonists as monotherapy or in combination treatments.

Conclusions:

  • TRAIL receptor agonists represent a promising therapeutic strategy for cancer treatment.
  • Despite some reported side effects in normal cells with certain TRAIL preparations, TRAIL receptor agonists offer a viable approach.
  • Further research and clinical evaluation of TRAIL-based therapies are warranted for effective cancer treatment.

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