On the TRAIL to successful cancer therapy? Predicting and counteracting resistance against TRAIL-based therapeutics.
On the TRAIL to successful cancer therapy? Predicting and counteracting resistance against TRAIL-based therapeutics.
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DOI：
10.1038/onc.2012.164
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发表时间：
2013-03-14
期刊：
影响因子：
8
通讯作者：
Ford HL
中科院分区：
文献类型：
--
作者：
Dimberg LY;Anderson CK;Camidge R;Behbakht K;Thorburn A;Ford HL
TRAIL和针对TRAIL死亡受体的激动抗体杀死肿瘤细胞，而对正常细胞几乎没有损害。目前，一些针对TRAIL受体的新药正在临床试验中。然而，TRAIL耐药是基于TRAIL治疗的常见障碍，并限制了这些药物的效率。在这篇综述文章中，我们讨论了TRAIL耐药的不同机制，以及如何预测和治疗规避这些机制。此外，我们提供了迄今为止进行的所有基于TRAIL的临床试验的简要概述。很明显，尽管TRAIL疗法的总体效果令人失望，但一小部分患者对TRAIL的反应非常好。我们认为，只有当我们找到有效的方法来选择那些最有可能从治疗中受益的患者时，靶向TRAIL死亡受体在癌症中的真正潜力才能实现。为了实现这一目标，确定可以帮助我们预测TRAIL敏感性的生物标志物至关重要。
TRAIL and agonistic antibodies against TRAIL death receptors kill tumor cells while causing virtually no damage to normal cells. Several novel drugs targeting TRAIL receptors are currently in clinical trials. However, TRAIL resistance is a common obstacle in TRAIL based therapy and limits the efficiency of these drugs. In this review article we discuss different mechanisms of TRAIL resistance and how they can be predicted and therapeutically circumvented. In addition, we provide a brief overview of all TRAIL based clinical trials conducted so far. It is apparent that although the effects of TRAIL therapy are disappointingly modest overall, a small subset of patients responds very well to TRAIL. We argue that the true potential of targeting TRAIL death receptors in cancer can only be reached when we find efficient ways to select for those patients that are most likely to benefit from the treatment. To achieve this, it is crucial to identify biomarkers that can help us predict TRAIL sensitivity.