Trailing TRAIL Resistance: Novel Targets for TRAIL Sensitization in Cancer Cells.
Trailing TRAIL Resistance: Novel Targets for TRAIL Sensitization in Cancer Cells.
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DOI：
10.3389/fonc.2015.00069
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发表时间：
2015
影响因子：
4.7
通讯作者：
Mishra DP
中科院分区：
文献类型：
--
作者：
Trivedi R;Mishra DP
对化疗药物的耐药性是癌症治疗成功的主要障碍。肿瘤坏死因子相关凋亡诱导配体（tumor necrosis factor-related apoptosis-inducing ligand， TRAIL）是肿瘤坏死因子（tumor necrosis factor， TNF）配体家族中的一员，通过与死亡受体DR4和DR5相互作用，启动癌细胞凋亡。TRAIL被认为是一种有吸引力的化疗药物，因为它可以特异性地靶向癌细胞，同时保留正常细胞。然而，TRAIL疗法有一个主要的局限性，因为大量的癌症对TRAIL产生耐药性并逃避免疫系统的破坏。因此，阐明TRAIL耐药的分子靶点和信号通路对于制定有效的TRAIL耐药癌症治疗策略至关重要。虽然导致TRAIL耐药的各种分子靶点已经得到了很好的研究，但最近的研究表明，一些关键的细胞过程对TRAIL耐药的贡献需要得到充分阐明。这些过程主要包括异常蛋白质合成、蛋白质错误折叠、泛素调节的死亡受体表达、代谢途径、表观遗传失调和转移。能够抑制这些缺陷细胞过程的新型合成/天然化合物可能会恢复TRAIL敏感性，并且与这些化合物联合治疗可能会使TRAIL耐药的癌细胞对TRAIL诱导的凋亡重新敏感。在这篇综述中，我们总结了与TRAIL耐药相关的关键细胞过程及其作为新型TRAIL增敏剂治疗靶点的地位。
Resistance to chemotherapeutic drugs is the major hindrance in the successful cancer therapy. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF) family of ligands, which initiates apoptosis in cancer cells through interaction with the death receptors DR4 and DR5. TRAIL is perceived as an attractive chemotherapeutic agent as it specifically targets cancer cells while sparing the normal cells. However, TRAIL therapy has a major limitation as a large number of the cancer develop resistance toward TRAIL and escape from the destruction by the immune system. Therefore, elucidation of the molecular targets and signaling pathways responsible for TRAIL resistance is imperative for devising effective therapeutic strategies for TRAIL resistant cancers. Although, various molecular targets leading to TRAIL resistance are well-studied, recent studies have implicated that the contribution of some key cellular processes toward TRAIL resistance need to be fully elucidated. These processes primarily include aberrant protein synthesis, protein misfolding, ubiquitin regulated death receptor expression, metabolic pathways, epigenetic deregulation, and metastasis. Novel synthetic/natural compounds that could inhibit these defective cellular processes may restore the TRAIL sensitivity and combination therapies with such compounds may resensitize TRAIL resistant cancer cells toward TRAIL-induced apoptosis. In this review, we have summarized the key cellular processes associated with TRAIL resistance and their status as therapeutic targets for novel TRAIL-sensitizing agents.
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DOI：
10.2217/14796694.2.4.493
发表时间：
2006-08-01
期刊：
Future oncology (London, England)
影响因子：
--
作者：
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通讯作者：
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影响因子：
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影响因子：
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影响因子：
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作者：
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DOI：
10.1016/j.biocel.2009.11.015
发表时间：
2010-02-01
影响因子：
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作者：
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