Significance of TRAIL/Apo-2 ligand and its death receptors in apoptosis and necroptosis signalling: Implications for cancer-targeted therapeutics.
Biochem Pharmacol
; 221: 116041, 2024 03.
Article
em En
| MEDLINE
| ID: mdl-38316367
ABSTRACT
The human immune defensesystem routinely expresses the tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), which is the most prevalent element for antitumor immunity. TRAIL associates with its death receptors (DRs), DR4 (TRAIL-R1), and DR5 (TRAIL-R2), in cancer cells to initiate the intracellular apoptosis cascade. Accordingly, numerous academic institutions and pharmaceutical companies havetried to exploreTRAIL's capacity to kill tumourcells by producing recombinant versions of it (rhTRAIL) or TRAIL receptor agonists (TRAs) [monoclonal antibody (mAb), synthetic and natural compounds, etc.] and molecules that sensitize TRAIL signalling pathway for therapeutic applications. Recently, several microRNAs (miRs) have been found to activate or inhibit death receptor signalling. Therefore, pharmacological regulation of these miRs may activate or resensitize the TRAIL DRs signal, and this is a novel approach for developing anticancer therapeutics. In this article, we will discuss TRAIL and its receptors and molecular pathways by which it induces various cell death events. We will unravel potential innovative applications of TRAIL-based therapeutics, and other investigated therapeutics targeting TRAIL-DRs and summarize the current preclinical pharmacological studies and clinical trials. Moreover, we will also emphasizea few situations where future efforts may be addressed to modulate the TRAIL signalling pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ligante Indutor de Apoptose Relacionado a TNF
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Biochem Pharmacol
/
Biochem. pharmacol
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Biochemical pharmacology
Ano de publicação:
2024
Tipo de documento:
Article