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Targeting TRAIL death receptors

C N A M Oldenhuis1, J H Stegehuis, A M E Walenkamp

  • 1Department of Medical Oncology, University Medical Center Groningen, The Netherlands.

Current Opinion in Pharmacology
|July 16, 2008
PubMed

Insights

Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) shows promise as an anticancer agent, particularly for glioblastomas. Combination therapies are being explored to enhance its effectiveness against resistant tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Development

Background:

  • Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) triggers apoptosis via death receptors.
  • Recombinant TRAIL and anti-TRAIL receptor antibodies are potential anticancer agents with low toxicity to normal cells.

Purpose of the Study:

  • To review current knowledge on TRAIL-based agents.
  • To highlight their potential in treating chemotherapy-resistant glioblastomas.
  • To discuss sensitization strategies using bortezomib.

Main Methods:

  • Review of existing literature on TRAIL and its analogs.
  • Analysis of early-phase clinical trial data.
  • Discussion of preclinical combination studies.

Main Results:

  • TRAIL-based agents demonstrate limited toxicity and some tumor responses in early clinical trials.
  • Glioblastomas are a key focus due to their intrinsic chemotherapy resistance.
  • Combination with bortezomib shows potential for sensitizing tumor cells.

Conclusions:

  • TRAIL-based therapies are promising anticancer agents in early development.
  • Combination strategies are crucial for overcoming resistance, especially in glioblastomas.
  • Further research into sensitizing mechanisms, like bortezomib co-administration, is warranted.

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