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Death receptor agonists as a targeted therapy for cancer

Jeffrey Wiezorek1, Pamela Holland, Jonathan Graves

  • 1Department of Global Development, Amgen Inc., Thousand Oaks, California 91320, USA. wiezorek@amgen.com

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|March 4, 2010
PubMed

Insights

Novel cancer therapies aim to reactivate apoptosis, programmed cell death, using tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) to selectively eliminate malignant cells. These death receptor agonists are in clinical trials, showing promise for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Apoptosis, or programmed cell death, is crucial for regulating cell numbers and removing damaged cells.
  • Dysregulation of apoptosis is a hallmark of human cancers.
  • Understanding programmed cell death pathways has led to novel therapeutic strategies targeting cancer cells.

Purpose of the Study:

  • To review the therapeutic potential of death receptor agonists, such as Apo2L/TRAIL, for cancer treatment.
  • To discuss the development of novel agents that reactivate apoptosis in malignant cells via the extrinsic pathway.
  • To summarize the current status of clinical evaluations and biomarker research for these agents.

Main Methods:

  • Review of scientific literature on apoptosis and cancer therapeutics.
  • Analysis of the extrinsic apoptosis pathway activated by Apo2L/TRAIL and death receptor agonists.
  • Examination of ongoing clinical trials and biomarker development for targeted cancer therapies.

Main Results:

  • Tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) and its agonists can selectively induce apoptosis in tumor cells.
  • Several therapeutics, including recombinant Apo2L/TRAIL and monoclonal antibodies targeting death receptors 4 or 5, are under investigation.
  • These agents are being evaluated in Phase 1 and 2 clinical trials, alone or in combination therapies.

Conclusions:

  • Death receptor agonists represent a promising therapeutic strategy for cancer by reactivating apoptosis.
  • Ongoing clinical trials and biomarker identification are critical for advancing these agents as effective cancer treatments.
  • Further research is needed to optimize patient selection and monitor response to Apo2L/TRAIL-based therapies.

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