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To kill a tumor cell: the potential of proapoptotic receptor agonists

Avi Ashkenazi1, Roy S Herbst

  • 1Genentech, South San Francisco, California 94080, USA. aa@gene.com

The Journal of Clinical Investigation
|June 5, 2008
PubMed

Insights

Dysregulation of apoptosis contributes to cancer. Proapoptotic receptor agonists (PARAs), like Apo2L/TRAIL, show promise for cancer therapy, potentially synergizing with existing treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Apoptosis, or programmed cell death, is crucial for preventing uncontrolled cell growth.
  • Defects in apoptosis pathways are a hallmark of cancer, driving tumorigenesis.
  • The extrinsic apoptosis pathway is a key target for novel cancer therapies.

Purpose of the Study:

  • To explore the therapeutic potential of proapoptotic receptor agonists (PARAs).
  • To investigate the role of recombinant human Apo2L/TRAIL and agonistic mAbs in cancer treatment.
  • To identify potential combination strategies and patient selection biomarkers for PARA therapy.

Main Methods:

  • Review of mechanistic and preclinical data for Apo2L/TRAIL.
  • Analysis of potential synergies with conventional cancer therapies.
  • Exploration of combining PARAs with molecularly targeted agents.

Main Results:

  • Preclinical data suggest Apo2L/TRAIL is a promising therapeutic candidate.
  • PARAs demonstrate potential for synergistic effects with conventional treatments.
  • Identification of novel molecular biomarkers could predict patient response to PARAs.

Conclusions:

  • Targeting the extrinsic apoptosis pathway with PARAs offers a promising therapeutic strategy.
  • Combination therapies involving PARAs may enhance treatment efficacy.
  • Biomarker discovery is essential for personalized PARA therapy in cancer patients.

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