TRAIL receptor signalling and modulation: Are we on the right TRAIL?

摘要: Tumour necrosis factor-related apoptosis-inducing ligand or Apo2 (TRAIL/Apo2L) is a member of the tumour factor (TNF) superfamily cytokines that induces apoptosis upon binding to its death domain-containing transmembrane receptors, receptors 4 and 5 (DR4, DR5). Importantly, TRAIL preferentially in cancer cells while exhibiting little no toxicity normal cells. To date, research has focused on mechanism induced by processes involved development resistance. TRAIL-resistant tumours can be re-sensitized combination with chemotherapeutics irradiation. Studies suggest many only one two death-inducing functional. These findings as well aim avoid decoy receptor-mediated neutralization led receptor-specific variants agonistic antibodies. molecules are predicted more potent than native vivo may suitable for targeted treatment particular tumours. This review focuses current status receptor-targeting therapy, apoptotic signalling pathway prognostic implications receptor expression modulation sensitivity therapies. The mechanisms resistance potential measures taken overcome them also addressed. Finally, clinical trials recombinant DR4-/DR5-specific antibodies pre-clinical studies receptor-selective discussed including obstacles facing use these anti-cancer therapeutics.