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Expert Opin Ther Targets. 2010 Oct;14(10):1091-108. doi: 10.1517/14728222.2010.519701.

TRAIL receptor signaling and therapeutics.

Author information

1
Penn State Hershey Medical Center, Penn State Hershey Cancer Institute, Penn State College of Medicine, Department of Medicine (Hematology/Oncology), Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Hershey, PA 17033, USA.

Abstract

IMPORTANCE OF THE FIELD:

TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines, which can induce apoptotic cell death in a variety of tumor cells by engaging specific death receptors, TRAIL-R1 and TRAIL-R2, while having low toxicity towards normal cells. There is interest in cancer therapy inducing cell death by activation of the death-receptor-mediated apoptotic pathway while avoiding decoy-receptor-mediated neutralization of the signal. This has led to the development of a number of receptor-specific TRAIL-variants and agonistic antibodies. Some of these soluble recombinant TRAIL and agonist antibodies targeting TRAIL-R1 and/or TRAIL-R2 are progressing in clinical trials. In addition, TRAIL-resistant tumors can be sensitized to TRAIL by a combination of TRAIL or agonistic antibodies with chemotherapeutic agents, targeted small molecules or irradiation.

AREAS COVERED IN THIS REVIEW:

Recent advances in developing TRAIL or its agonist receptor antibodies in cancer therapy. We also discuss combination therapies in overcoming TRAIL resistance in cancer cells.

WHAT THE READER WILL GAIN:

Knowledge of current clinical trials, the promise and obstacles in the future development of therapies affecting TRAIL signaling pathways.

TAKE HOME MESSAGE:

Cancer therapeutics targeting the TRAIL/TRAIL receptor signaling pathway hold great promise for molecularly targeted pro-apoptotic anti-cancer therapy.

PMID:
20819019
DOI:
10.1517/14728222.2010.519701
[Indexed for MEDLINE]

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