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Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
09:53

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens

Published on: February 6, 2017

Death receptors as targets in cancer

O Micheau1, S Shirley, F Dufour

  • 1UMR866, INSERM, Dijon, France. olivier.micheau@inserm.fr

British Journal of Pharmacology
|May 4, 2013
PubMed
Abstract

Insights

Anti-cancer therapies using TNF-related apoptosis-inducing ligand (TRAIL) agonists have shown limited success. This review explores reasons for TRAIL therapy

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Development

Background:

  • Anti-tumour therapies utilizing pro-apoptotic receptor agonists, such as TNF-related apoptosis-inducing ligand (TRAIL) or antibodies targeting TRAIL-R1/TRAIL-R2, have yielded disappointing clinical outcomes.
  • Despite demonstrated clinical activity and a favorable safety profile, these TRAIL-based strategies have not met expectations in cancer treatment.
  • This review is part of a themed section on Emerging Therapeutic Aspects in Oncology.

Purpose of the Study:

  • To discuss potential reasons behind the limited success of current TRAIL-based anti-cancer therapies.
  • To provide insights for designing optimized therapeutic protocols for future clinical trials.
  • To enhance the understanding of TNF-related apoptosis-inducing ligand (TRAIL) signaling regulation and resistance mechanisms.

Main Methods:

  • Review of existing literature on TNF-related apoptosis-inducing ligand (TRAIL) signaling pathways.
  • Analysis of clinical trial data and preclinical studies investigating TRAIL agonists and antibodies.
  • Discussion of mechanisms regulating TRAIL-induced apoptosis and resistance.

Main Results:

  • Identified several factors contributing to the lack of efficacy of TRAIL-based therapies.
  • Highlighted the complexity of TRAIL signaling and the development of resistance mechanisms in cancer cells.
  • Provided a framework for understanding the discrepancies between preclinical promise and clinical outcomes.

Conclusions:

  • Revisiting the understanding of TRAIL signaling and resistance is crucial for improving anti-cancer therapy.
  • Rational design of future clinical trials incorporating TRAIL-based strategies requires a deeper mechanistic insight.
  • Optimized protocols may enhance the therapeutic potential of TRAIL agonists and antibodies in oncology.
Keywords:
FasTNF-receptor superfamilyTRAILapoptosisresistancetherapytumour targeting

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