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Death receptors as targets for anti-cancer therapy

Kerstin Papenfuss1, Stefanie M Cordier, Henning Walczak

  • 1Tumour Immunology Unit, Division of Medicine, Imperial College London, United Kingdom.

Journal of Cellular and Molecular Medicine
|February 13, 2009
PubMed

Insights

This review explores using death receptors to trigger cancer cell death, bypassing resistance to traditional chemotherapy. It summarizes research on key death receptors and their therapeutic applications in clinical trials.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Human tumor cells evade normal growth, division, and death regulation.
  • Classical chemotherapy induces apoptosis via DNA damage, but many tumors are resistant due to mutations (e.g., p53).

Purpose of the Study:

  • To review current knowledge of key death receptors (TNF-R1, CD95, TRAIL-R1, TRAIL-R2) for cancer therapy.
  • To summarize preclinical strategies targeting these receptors.
  • To provide an overview of their clinical trial applications.

Main Methods:

  • Literature review of death receptor superfamily members.
  • Analysis of preclinical anti-cancer approaches using death receptors.
  • Summary of clinical trial data for death receptor-targeted therapies.

Main Results:

  • Death receptors offer a strategy to induce apoptosis externally, circumventing intracellular resistance mechanisms.
  • Several death receptors, including TNF-R1, CD95, TRAIL-R1, and TRAIL-R2, are prominent targets.
  • Preclinical studies and ongoing clinical trials are evaluating these receptors for cancer treatment.

Conclusions:

  • Targeting death receptors presents a promising avenue to overcome chemotherapy resistance in cancer.
  • Further clinical investigation is warranted to fully realize the therapeutic potential of death receptor agonists.

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