Targeting TRAIL in the treatment of cancer: new developments. (September 2015)

• Record Type: Journal Article
• Authors: Lim, Bora; Allen, Joshua E; Prabhu, Varun V; Talekar, Mala K; Finnberg, Niklas K; El-Deiry, Wafik S
• Is Part Of: Expert opinion on therapeutic targets. Volume 19:Number 9(2015:Sep.)
• Page Start: 1171
• Page End: 1185
• Publication Date: 2015-09
• Subjects: Drugs -- Research -- Periodicals; 615.072
• Languages: English
• ISSNs: 1744-7631

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold> <italic>Introduction:</italic> </bold> 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.</p> <p> <bold> <italic>Areas covered:</italic> </bold> 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.</p> <p> <bold> <italic>Expert opinion:</italic> </bold> 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.</p> </abstract>