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Targeting death receptors in cancer with Apo2L/TRAIL

Sean K Kelley1, Avi Ashkenazi

  • 1Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. skelley@gene.com

Current Opinion in Pharmacology
|July 15, 2004
PubMed

Insights

Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) induces cancer cell death independently of p53. This promising cancer therapeutic shows single-agent activity and enhances chemotherapy or radiotherapy efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Conventional cancer therapeutics often rely on the p53 tumor suppressor gene, which is frequently inactivated in tumors.
  • Death receptor ligands offer an alternative therapeutic strategy by triggering apoptosis independently of p53.
  • Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is a specific death receptor ligand with potential anti-cancer properties.

Purpose of the Study:

  • To evaluate the therapeutic potential of Apo2L/TRAIL as a cancer treatment.
  • To assess the efficacy of Apo2L/TRAIL as a single agent and in combination with conventional therapies.
  • To investigate the mechanisms of Apo2L/TRAIL-induced apoptosis in cancer cells.

Main Methods:

  • In vitro studies using various cancer cell lines to assess Apo2L/TRAIL-induced apoptosis.
  • In vivo studies using tumor xenograft mouse models to evaluate Apo2L/TRAIL efficacy.
  • Combination studies with chemotherapy and radiotherapy in preclinical models.

Main Results:

  • Apo2L/TRAIL effectively induced apoptosis in diverse cancer cell lines with minimal toxicity to normal cells.
  • Apo2L/TRAIL demonstrated single-agent anti-tumor activity in preclinical models.
  • Apo2L/TRAIL synergized with chemotherapy and radiotherapy, enhancing tumor regression.

Conclusions:

  • Apo2L/TRAIL represents a promising therapeutic agent for various cancers, particularly those resistant to conventional treatments.
  • Its ability to induce apoptosis independently of p53 makes it valuable for a wide range of malignancies.
  • Apo2L/TRAIL holds potential for augmenting current cancer treatment strategies.

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