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Exploring the TRAILs less travelled: TRAIL in cancer biology and therapy

Silvia von Karstedt1,2, Antonella Montinaro1, Henning Walczak1

  • 1Centre for Cell Death, Cancer and Inflammation, UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6DD, UK.

Nature Reviews. Cancer
|May 25, 2017
PubMed

Insights

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows promise for cancer treatment by inducing cancer cell death. However, overcoming TRAIL resistance and its pro-tumorigenic effects are key challenges for effective cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce cancer cell apoptosis with low toxicity.
  • Biotherapeutic TRAIL receptor (TRAIL-R) agonists have shown disappointing clinical trial outcomes.
  • Cancers can develop TRAIL resistance and utilize the TRAIL-TRAIL-R system for tumor growth.

Purpose of the Study:

  • To review the current understanding of TRAIL-TRAIL-R system biology.
  • To identify gaps in knowledge regarding TRAIL signaling in cancer.
  • To discuss strategies for overcoming TRAIL resistance and countering pro-tumorigenic effects.

Main Methods:

  • Literature review of TRAIL and TRAIL-R signaling pathways.
  • Analysis of clinical trial data for TRAIL-R agonists.
  • Assessment of mechanisms of TRAIL resistance in cancer.
  • Evaluation of endogenous TRAIL system's role in tumorigenesis.

Main Results:

  • Despite initial promise, TRAIL-based therapies face significant challenges due to cancer resistance.
  • The endogenous TRAIL system can be co-opted by tumors to promote their own survival and growth.
  • Novel insights suggest potential strategies to overcome resistance and target the TRAIL pathway.

Conclusions:

  • Harnessing the TRAIL-TRAIL-R system for cancer treatment requires overcoming resistance mechanisms.
  • Understanding and countering the pro-tumorigenic roles of endogenous TRAIL are crucial.
  • Further research into TRAIL biology and targeted therapies offers hope for effective cancer treatment.

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