Format

Send to

Choose Destination
Expert Opin Ther Targets. 2015;19(9):1171-85. doi: 10.1517/14728222.2015.1049838. Epub 2015 May 25.

Targeting TRAIL in the treatment of cancer: new developments.

Author information

1
The University of Texas MD Anderson Cancer Center, Department of Cancer Medicine, Breast Medical Oncology , Houston, TX 77030 , USA.

Abstract

INTRODUCTION:

While apoptosis is critical for maintaining homeostasis in normal cells, defective apoptosis contributes to the survival of cancer cells. TNF-related apoptosis-inducing ligand (TRAIL)-targeted therapy has attracted significant effort for treating cancer, but the clinical results have revealed limitations. The authors review the current status of development of TRAIL-targeted therapy with an outlook towards the future.

AREAS COVERED:

Recombinant human proteins, small molecules and agonistic monoclonal antibodies targeting death receptors that trigger TRAIL-mediated apoptosis are covered in this article. The authors review both intrinsic and extrinsic apoptotic pathways, highlighting how the apoptosis serves as a promising therapeutic target. They also review different categories of TRAIL pathway targeting agents and provide a brief overview of clinical trials using these agents. The authors discuss the limitations of conventional approaches for targeting the TRAIL pathway as well as future directions.

EXPERT OPINION:

The development of better combination partners for pro-apoptotic TRAIL pathway modulators including novel agents inhibiting anti-apoptotic molecules or targeting alternative resistance pathways may improve the chances for anti-tumor responses in the clinic. Developing predictive biomarkers via circulating tumor cells/DNA, apoptosis signal products, and genetic signatures/protein biomarkers from tumor tissue are also suggested as future directions.

KEYWORDS:

TRAIL; apo2L; apoptosis; cancer therapy; extrinsic pathway; intrinsic pathway; novel therapeutics; targeting apoptosis pathway

PMID:
26004811
DOI:
10.1517/14728222.2015.1049838
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Taylor & Francis
Loading ...
Support Center