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Targeting the extrinsic apoptosis signaling pathway for cancer therapy

Thomas J Sayers1

  • 1SAIC-Frederick, Inc., Laboratory of Experimental Immunology, Center for Cancer Research, Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702-1201, USA. sayerst@mail.nih.gov

Cancer Immunology, Immunotherapy : CII
|June 1, 2011
PubMed

Insights

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows promise in cancer therapy, but many cancer cells resist its effects. Researchers are exploring compounds like bortezomib to enhance TRAIL-induced apoptosis for improved cancer treatment.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • The extrinsic apoptosis pathway is activated by tumor necrosis factor (TNF) family ligands binding to death receptors (DRs).
  • TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells with minimal toxicity, making it a therapeutic candidate.
  • Many cancer cells exhibit resistance to TRAIL-induced apoptosis, necessitating strategies to overcome this resistance.

Purpose of the Study:

  • To review the signaling mechanisms of TRAIL-mediated apoptosis.
  • To discuss agents that sensitize cancer cells to TRAIL, focusing on bortezomib and novel compounds.
  • To explore alternative administration methods for TRAIL and its agonists and identify research gaps.

Main Methods:

  • Review of existing literature on TRAIL apoptosis signaling.
  • Discussion of preclinical studies on apoptosis-sensitizing agents, including proteasome inhibitors.
  • Exploration of novel sensitizers and therapeutic delivery strategies for TRAIL and DR agonists.

Main Results:

  • TRAIL demonstrates preferential apoptosis induction in transformed cells.
  • Bortezomib and other identified agents can sensitize resistant cancer cells to TRAIL.
  • Alternative administration routes for TRAIL and DR agonists are being investigated.

Conclusions:

  • TRAIL holds significant therapeutic potential in oncology, but overcoming resistance is crucial.
  • Combination therapies involving TRAIL and apoptosis-sensitizing agents like bortezomib are promising for cancer treatment.
  • Further research into TRAIL signaling and novel sensitizers is needed to optimize extrinsic apoptosis pathway targeting for cancer therapy.

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