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Targeting the Apo2L/TRAIL system for the therapy of autoimmune diseases and cancer

Luis Martinez-Lostao1, Isabel Marzo, Alberto Anel

  • 1Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain. lumartin@unizar.es

Biochemical Pharmacology
|January 11, 2012
PubMed

Insights

Apo 2 ligand/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL) therapy shows promise for cancer and inflammatory diseases by selectively inducing cell death. Combined therapies enhance Apo2L/TRAIL effectiveness against resistant tumors.

Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • Apo 2 ligand/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL) is a cytokine that induces apoptosis via death receptors DR4/DR5.
  • The Apo2L/TRAIL system is a promising therapeutic target due to its cancer cell selectivity and low toxicity to normal cells.
  • Emerging research indicates potential applications in treating inflammatory disorders like rheumatoid arthritis.

Purpose of the Study:

  • To review the current status of Apo2L/TRAIL-based therapies.
  • To discuss the therapeutic potential and limitations of Apo2L/TRAIL in human diseases.
  • To explore combined therapeutic strategies involving Apo2L/TRAIL.

Main Methods:

  • Development of receptor-specific Apo2L/TRAIL molecular variants.
  • Creation of agonistic monoclonal antibodies targeting Apo2L/TRAIL.
  • Investigation of Apo2L/TRAIL sensitization by chemotherapeutic agents.

Main Results:

  • Several Apo2L/TRAIL variants and antibodies are in clinical trials.
  • Apo2L/TRAIL demonstrates efficacy against various cancer cell types.
  • Chemotherapeutic agents can sensitize Apo2L/TRAIL-resistant tumors, enabling combination therapies.

Conclusions:

  • Apo2L/TRAIL-based therapies offer significant promise for treating cancer and inflammatory conditions.
  • Further research and clinical trials are necessary to fully realize the therapeutic potential and address limitations.
  • Combined therapeutic approaches hold potential for overcoming resistance and improving treatment outcomes.

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