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TRAIL: a sword for killing tumors
1State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University School of Life Sciences, Shanghai, PR China. shulinwang@fudan.edu.cn
Abstract:
Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising anticancer agent that selectively triggers apoptosis in various cancer cells by interacting with its proapoptotic receptors DR4 and KILLER/DR5. The intensive studies of TRAIL signaling pathways over the past decade have provided clues for understanding the molecular mechanisms of TRAIL-induced apoptosis in carcinogenesis and identified an array of therapeutic responses elicited by TRAIL and its receptor agonists. Preclinical and clinical studies have shown that recombinant TRAIL and the agonistic mono-antibodies targeting TRAIL receptors exhibit potent tumoricidal activities as monotherapies and that the combinatorial therapies of these agents in conjunction with other anticancer modalities such as chemo or radiotherapy amplify the activities of anticancer agents and widen the therapeutic window by overcoming tumor resistance to apoptosis and driving cancer cells to self-destruction. The identification of a number of biomarkers that predict tumor sensitivity of patients to TRAIL-based therapy shed a new light on the personalized therapeutic strategies targeting the TRAIL/TRAIL receptor pathway.
Insights
Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) shows promise as an anticancer agent. TRAIL-based therapies, including combinations, effectively target cancer cells by inducing apoptosis, with biomarkers guiding personalized treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells via DR4 and KILLER/DR5 receptors.
- Decade-long research elucidates TRAIL signaling in carcinogenesis and therapeutic responses.
Purpose of the Study:
- To review the therapeutic potential of TRAIL and its receptor agonists in cancer treatment.
- To highlight the role of TRAIL signaling in overcoming apoptosis resistance and enhancing anticancer efficacy.
Main Methods:
- Review of preclinical and clinical studies on recombinant TRAIL and agonistic antibodies.
- Analysis of combinatorial therapies involving TRAIL-based agents with chemotherapy or radiotherapy.
- Examination of biomarkers predicting patient response to TRAIL-based therapies.
Main Results:
- Recombinant TRAIL and TRAIL receptor agonists demonstrate potent tumoricidal activity as monotherapies.
- Combinatorial therapies amplify anticancer agent activity and broaden the therapeutic window.
- Biomarkers are identified for predicting tumor sensitivity to TRAIL-based treatments.
Conclusions:
- TRAIL-based therapies offer significant anticancer potential, both as monotherapies and in combination regimens.
- Targeting the TRAIL/TRAIL receptor pathway is crucial for overcoming apoptosis resistance in cancer.
- Biomarker discovery enables personalized therapeutic strategies for TRAIL-based treatments.
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