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License to kill tumors: how much hope is justified for trail?
1Biochemistry Section, Surgical Neurology Branch, NINDS, NIH, Bethesda 20892, USA. frankst@ninds.nih.gov
Abstract:
In 1995, a new cytokine termed TRAIL (tumor necrosis factor--related apoptosis-inducing ligand) was discovered and demonstrated to selectively induce programmed cell death in transformed cell lines. Preclinical cytotoxicity studies in mice and nonhuman primates have produced promising results by demonstrating that TRAIL exerts potent tumoricidal activity but lacks severe toxicity towards normal tissues making it a potentially ideal candidate for cancer therapy. This article reviews aspects of our current understanding of TRAIL signaling pathways and summarizes how this knowledge is currently being translated into TRAIL-based tumor-selective therapeutic strategies.
Insights
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills cancer cells with minimal toxicity to normal tissues. This review explores TRAIL
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Discovery of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) in 1995.
- TRAIL's selective induction of programmed cell death (apoptosis) in cancer cells.
- Potential of TRAIL as a targeted cancer therapeutic agent.
Purpose of the Study:
- To review current understanding of TRAIL signaling pathways.
- To summarize the translation of TRAIL knowledge into therapeutic strategies.
- To highlight TRAIL's tumor-selective activity and low toxicity.
Main Methods:
- Review of preclinical cytotoxicity studies in animal models (mice and nonhuman primates).
- Analysis of TRAIL signaling mechanisms.
- Examination of current TRAIL-based therapeutic strategies.
Main Results:
- TRAIL demonstrates potent tumoricidal activity in preclinical studies.
- TRAIL exhibits minimal toxicity towards normal tissues.
- Promising results support TRAIL's potential as an ideal cancer therapy candidate.
Conclusions:
- TRAIL signaling pathways are crucial for its therapeutic potential.
- TRAIL-based strategies are being developed for tumor-selective cancer treatment.
- TRAIL represents a promising avenue for novel cancer therapies.