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Targeting TRAIL towards the clinic

Devalingam Mahalingam1, Corina N A M Oldenhuis, Eva Szegezdi

  • 1Cancer Research and Therapy Center, University of Texas Health Science Center, San Antonio, TX 78229, USA. mahalingam@uthscsa.edu

Current Drug Targets
|July 23, 2011
PubMed

Insights

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows promise as a cancer therapy due to its selective toxicity. Strategies to overcome TRAIL resistance are crucial for enhancing its clinical efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a TNF superfamily member inducing apoptosis via death receptors.
  • TRAIL exhibits preferential toxicity to cancer cells, making it a potential therapeutic agent.
  • TRAIL activates key signaling pathways including JNK, ERK, Akt, and NF-κB.

Purpose of the Study:

  • To review TRAIL receptor-targeting as an anticancer therapy.
  • To discuss TRAIL-induced apoptotic signaling pathways and prognostic implications.
  • To address TRAIL resistance mechanisms and combination strategies.

Main Methods:

  • Literature review focusing on TRAIL receptor biology and therapy.
  • Analysis of signaling cascades activated by TRAIL.
  • Examination of clinical trial progress for TRAIL-based therapies.

Main Results:

  • TRAIL induces apoptosis through the extrinsic pathway but faces resistance in some cancer cells.
  • Combination therapies can overcome TRAIL resistance.
  • Agonistic antibodies targeting TRAIL receptors (DR4/DR5) are in clinical trials.

Conclusions:

  • TRAIL receptor-targeting holds significant therapeutic potential in oncology.
  • Understanding and overcoming TRAIL resistance is key to clinical success.
  • Development of novel TRAIL variants and antibodies offers future directions for apoptosis-inducing cancer therapy.

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