TRAIL in the Treatment of Cancer: From Soluble Cytokine to Nanosystems

Abstract

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.

BSV163/DOPE‐mediated TRAIL gene transfection acts synergistically with chemotherapy against cisplatin‐resistant ovarian cancer

“…The binding of TRAIL to its DR4 and DR5 is the first step to induce cell death signaling (Alizadeh Zeinabad & Szegezdi, 2022). Therefore, the presence of these receptors on the cell surface indicates cancer cells' susceptibility to TRAIL death signaling.…”

“…It has been well established that the activation of caspase 8 is crucial for TRAIL‐induced cell death signaling pathways (Alizadeh Zeinabad & Szegezdi, 2022). Based on this premise, we measured caspase 8 activity in cisplatin‐sensitive and ‐resistant ovarian cancer cells following different treatments.…”

“…FADD in turn recruits the pro‐caspase‐8 through its N‐terminal death effector domain. The assemblage of DR, FADD and pro‐caspase‐8 is known as the death‐inducing signaling complex (DISC) (Alizadeh Zeinabad & Szegezdi, 2022). The effective oligomerization of DR and FADD is of particular importance in activating pro‐caspase‐8 and transducing an efficient death signal (Muppidi et al, 2006; Yan et al, 2013).…”

“…Tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) belongs to the TNF cytokine superfamily. Its extracellular domain can be cleaved by proteases releasing a soluble and functional form (Alizadeh Zeinabad & Szegezdi, 2022). TRAIL induces cell death upon ligation with its death receptors (Singh et al, 2021).…”

Extraction of echinacoside from Cistanche tubulosa (Schenk) R. Wight and investigation of its protective effect on liver injury in sepsis rats

“…It is an important proinflammatory cytokine (Singh et al, 2021). TNF-α is one of the most important inflammatory mediators, which can activate the inflammatory cascade reaction and participate in regulating the apoptosis pathway and inducing multi-tissue cell damage (Alizadeh Zeinabad & Szegezdi, 2022). IL-6 is a multifunctional cytokine, which can induce the production of other harmful inflammatory factors, increase the liver load, and participate in the liver injury (Unver & McAllister, 2018).…”