From biochemical principles of apoptosis induction by TRAIL to application in tumour therapy.
The tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily which has been shown to selectively kill tumour cells, while sparing normal tissue. This attribute makes TRAIL an attractive drug candidate for cancer therapy. Although most primary tumour cells turned out to be primarily TRAIL-resistant, recent studies evidenced that a variety of cancers can be sensitised to TRAIL-induced apoptosis upon pre-treatment with chemotherapeutic agents or irradiation, while normal cells remain TRAIL-resistant. However, biomarkers that reliably predict which patients may benefit from such combinatorial therapies are required. Thus, it is essential to better understand the mechanisms underlying TRAIL resistance versus sensitivity. In this chapter, we introduce the signalling events which take place during TRAIL-induced apoptosis, describe the physiological function of TRAIL and summarise pre-clinical and clinical results obtained so far with TRAIL-receptor agonists.
Cordier
Stefanie M
SM
Tumour Immunology Unit, Division of Medicine, Imperial College, London, W12 0NN, UK.
Papenfuss
Kerstin
K
Walczak
Henning
H
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism / Q000627:therapeutic use*
D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human