Revisiting the role of TRAIL/TRAIL-R in cancer biology and therapy

被引：28
|
作者：
Singh, Deepika [1 ]
Tewari, Mallika [2 ]
Singh, Sunita [3 ]
Narayan, Gopeshwar [1 ]
机构：
[1] Banaras Hindu Univ, Inst Sci, Dept Mol & Human Genet, Canc Genet Lab, Varanasi 221005, Uttar Pradesh, India
[2] Banaras Hindu Univ, Inst Med Sci, Dept Surg Oncol, Varanasi 221005, Uttar Pradesh, India
[3] Banaras Hindu Univ, Dept Zool, Mahila Mahavidyalaya, Varanasi 221005, Uttar Pradesh, India
来源：
FUTURE ONCOLOGY | 2021年 / 17卷 / 05期
关键词：
apoptosis; cancer therapy; clinical trials; decoy receptors; gene therapy; resistance; death receptors; TNFRSF superfamily; TRAIL; TRAIL-R; APOPTOSIS-INDUCING LIGAND; DEATH RECEPTOR 5; TRAIL-INDUCED APOPTOSIS; CELL LUNG-CANCER; NF-KAPPA-B; DR5; MONOCLONAL-ANTIBODY; UP-REGULATION; IN-VIVO; MEDIATED APOPTOSIS; ANTITUMOR-ACTIVITY;
D O I：
10.2217/fon-2020-0727
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, can induce apoptosis in cancer cells, sparing normal cells when bound to its associated death receptors (DR4/DR5). This unique mechanism makes TRAIL a potential anticancer therapeutic agent. However, clinical trials of recombinant TRAIL protein and TRAIL receptor agonist monoclonal antibodies have shown disappointing results due to its short half-life, poor pharmacokinetics and the resistance of the cancer cells. This review summarizes TRAIL-induced apoptotic and survival pathways as well as mechanisms leading to apoptotic resistance. Recent development of methods to overcome cancer cell resistance to TRAIL-induced apoptosis, such as protein modification, combination therapy and TRAIL-based gene therapy, appear promising. We also discuss the challenges and opportunities in the development of TRAIL-based therapies for the treatment of human cancers.
引用
收藏
页码：581 / 596
页数：16
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