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.
Original language | English (US) |
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Pages (from-to) | 1171-1185 |
Number of pages | 15 |
Journal | Expert Opinion on Therapeutic Targets |
Volume | 19 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2 2015 |
Keywords
- Apo2L
- TRAI
- apoptosis
- cancer therapy
- extrinsic pathway
- intrinsic pathway
- novel therapeutics
- targeting apoptosis pathway
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology
- Drug Discovery
- Clinical Biochemistry