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Updated: Jul 6, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

TRAIL receptor-targeted therapeutics: resistance mechanisms and strategies to avoid them

Andrew Thorburn1, Kian Behbakht, Heide Ford

  • 1Department of Pharmacology, University of Colorado Denver, School of Medicine, Aurora, CO 80010, USA. Andrew.Thorburn@uchsc.edu

Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
|April 1, 2008
PubMed

Insights

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor agonists show promise for cancer therapy by inducing tumor cell death. However, resistance mechanisms can limit their effectiveness, necessitating identification of biomarkers and strategies to overcome this resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Development

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors are key targets for cancer therapy due to their ability to induce apoptosis in cancer cells with minimal toxicity to normal tissues.
  • Several therapeutic agents, including recombinant TRAIL and agonistic antibodies, have been developed to activate these receptors and are currently undergoing clinical trials.

Purpose of the Study:

  • To review recent findings on mechanisms of resistance to TRAIL receptor-targeted cancer therapies.
  • To identify potential biomarkers for predicting TRAIL resistance in patients.
  • To explore strategies for overcoming TRAIL resistance and resensitizing tumors to treatment.

Main Methods:

  • Literature review of in vitro and in vivo studies on TRAIL receptor agonists and resistance mechanisms.
  • Analysis of data on potential biomarkers such as Six1, GALNT14, XIAP, and microRNAs.
  • Synthesis of information on therapeutic strategies to circumvent resistance.

Main Results:

  • Resistance to TRAIL receptor agonists can emerge through various mechanisms, potentially limiting clinical efficacy.
  • Specific biomarkers including Six1, GALNT14, XIAP, and certain microRNAs have been implicated in TRAIL resistance.
  • Strategies to overcome resistance and resensitize tumors are being investigated.

Conclusions:

  • Understanding TRAIL resistance mechanisms is crucial for optimizing cancer therapy.
  • Biomarker identification can aid in patient selection for TRAIL-targeted treatments.
  • Developing methods to circumvent resistance is essential for improving treatment outcomes in cancer patients.

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