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

被引：31

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

页码：581 / 596

页数：16

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