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. 2014 May;7(5):1327-1332.
doi: 10.3892/ol.2014.1922. Epub 2014 Feb 27.

TRAIL combinations: The new 'trail' for cancer therapy (Review)

Alaa Refaat  1 , Ahmed Abd-Rabou  1 , Asmaa Reda  1
Affiliations

TRAIL combinations: The new 'trail' for cancer therapy (Review)

Alaa Refaat et al. Oncol Lett. 2014 May.

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy is anticipated to be one of the most effective cancer treatments. However, resistance to TRAIL therapy remains a challenge facing the development of anticancer strategies. To circumvent this problem, TRAIL combinations have been experimented with for over ten years to induce synergism or sensitize resistant cancer cells. By analyzing the signaling pathways triggered by these combinations, this review has defined a set of core targets for novel combinatorial treatments. The review suggests specific pathways to be targeted together with TRAIL for more efficient treatment, including cellular FLICE inhibitory protein and its downstream survival factors, the Bcl-2 family and other prominent targets. The suggested pathways provide new avenues for more effective TRAIL-based cancer therapy.

Keywords: apoptosis; cancer therapy; death receptor 5; tumor necrosis factor related apoptosis-inducing ligand.

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Figures

Figure 1
Figure 1
Dual opposing signaling pathways of TRAIL. (A) The apoptotic signaling pathway. (B) The resistance pathway developed against TRAIL-induced apoptosis. TRAIL, tumor necrosis factor-related apoptosis-inducing ligand.
Figure 2
Figure 2
Signaling pathway of TRAIL/drug combinations. TRAIL, tumor necrosis factor-related apoptosis-inducing ligand.
Figure 3
Figure 3
Schematic diagram showing possible targets as part of future tumor necrosis factor-related apoptosis-inducing ligand-based therapies enhancing apoptosis. (A) Targeting C FLIP and downstream survival factors. (B) Targeting the Bcl 2 family. (C) manipulating p53 and STAT3.
See this image and copyright information in PMC

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