von Karstedt, S;
Montinaro, A;
Walczak, H;
(2017)
Exploring the TRAILs less travelled: TRAIL in cancer biology and therapy.
Nature Reviews Cancer
, 17
(6)
pp. 352-366.
10.1038/nrc.2017.28.
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Abstract
The discovery that the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis of cancer cells without causing toxicity in mice has led to the in-depth study of pro-apoptotic TRAIL receptor (TRAIL-R) signalling and the development of biotherapeutic drug candidates that activate TRAIL-Rs. The outcome of clinical trials with these TRAIL-R agonists has, however, been disappointing so far. Recent evidence indicates that many cancers, in addition to being TRAIL resistant, use the endogenous TRAIL–TRAIL-R system to their own advantage. However, novel insight on two fronts — how resistance of cancer cells to TRAIL-based pro-apoptotic therapies might be overcome, and how the pro-tumorigenic effects of endogenous TRAIL might be countered — gives reasonable hope that the TRAIL system can be harnessed to treat cancer. In this Review we assess the status quo of our understanding of the biology of the TRAIL–TRAIL-R system — as well as the gaps therein — and discuss the opportunities and challenges in effectively targeting this pathway.
| Type: | Article |
|---|---|
| Title: | Exploring the TRAILs less travelled: TRAIL in cancer biology and therapy |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/nrc.2017.28 |
| Publisher version: | https://doi.org/10.1038/nrc.2017.28 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Oncology, APOPTOSIS-INDUCING LIGAND, DEATH RECEPTOR 5, NF-KAPPA-B, NECROSIS-FACTOR RECEPTOR, REGULATORY T-CELLS, MEDIATED APOPTOSIS, TUMOR-GROWTH, MONOCLONAL-ANTIBODY, ANTITUMOR-ACTIVITY, MOLECULAR-CLONING |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10050108 |
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