TRAIL in the Treatment of Cancer: From Soluble Cytokine to Nanosystems
- Cancers (Basel). 2022 Oct 19;14(20):5125. doi: 10.3390/cancers14205125.
- 1. Apoptosis Research Centre, Biomedical Sciences Building, School of Biological and Chemical Sciences, University of Galway, H91 W2TY Galway, Ireland.
- 2. Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, University of Galway, H91 W2TY Galway, Ireland.
The death ligand tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF cytokine superfamily, has long been recognized for its potential as a Cancer therapeutic due to its low toxicity against normal cells. However, its translation into a therapeutic molecule has not been successful to date, due to its short in vivo half-life associated with insufficient tumor accumulation and resistance of tumor cells to TRAIL-induced killing. Nanotechnology has the capacity to offer solutions to these limitations. This review provides a perspective and a critical assessment of the most promising approaches to realize TRAIL's potential as an Anticancer therapeutic, including the development of fusion constructs, encapsulation, nanoparticle functionalization and tumor-targeting, and discusses the current challenges and future perspectives.