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Resistance to TRAIL and how to surmount it

Danijela Maksimovic-Ivanic1, Stanislava Stosic-Grujicic, Ferdinando Nicoletti

  • 1Department of Immunology, Institute for Biological Research Sinisa Stankovic, Belgrade University, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.

Immunologic Research
|March 13, 2012
PubMed

Insights

Tumor cells resist TRAIL-induced toxicity through receptor changes or signaling issues. This review explores strategies to restore TRAIL sensitivity and enhance immune cell efficiency in cancer therapy.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Tumor cells develop resistance to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-induced toxicity as a survival mechanism.
  • Resistance pathways include altered receptor expression (functional or decoy) and intracellular signaling defects.
  • This resistance hinders effective anti-cancer immune responses.

Purpose of the Study:

  • To review mechanisms by which tumor cells evade TRAIL-mediated apoptosis.
  • To explore therapeutic strategies for overcoming TRAIL resistance.
  • To suggest novel approaches for enhancing immune cell efficacy in cancer treatment.

Main Methods:

  • Literature review of studies on TRAIL resistance mechanisms in cancer.
  • Analysis of drug-induced sensitization to TRAIL (cytostatic and noncytostatic agents).
  • Examination of intracellular and membrane-level signaling pathways involved in TRAIL resistance.

Main Results:

  • Various drugs, including protease inhibitors and NO-hybridized molecules, can restore TRAIL sensitivity.
  • Reconstitution of sensitivity involves modulating specific membrane and intracellular signals.
  • Understanding these pathways is crucial for developing effective combination therapies.

Conclusions:

  • Targeting resistance mechanisms can re-sensitize tumors to TRAIL-induced apoptosis.
  • Novel strategies can reset immune cell efficiency for improved cancer treatment outcomes.
  • Combination therapies hold promise for overcoming TRAIL resistance and enhancing anti-cancer immunity.

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