Exploiting vulnerabilities in cancer signalling networks to combat targeted therapy resistance.
Exploiting vulnerabilities in cancer signalling networks to combat targeted therapy resistance.
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DOI：
10.1042/ebc20180016
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发表时间：
2018-10-26
影响因子：
6.4
通讯作者：
Huang PH
中科院分区：
文献类型：
--
作者：
Harrison PT;Huang PH
耐药性仍然是当今精准肿瘤学面临的最大挑战之一。尽管癌细胞采用了大量的耐药机制来破坏靶向治疗的效果，但对癌症信号网络的深入了解已经导致了在一线和挽救治疗环境中解决耐药问题的新策略的发展。在这篇综述中，我们简要概述了靶向治疗的主要耐药机制，包括信号重编程和肿瘤进化；我们的讨论还侧重于使用不同形式的综合疗法（如抑制剂组合、多靶点激酶抑制剂和HSP90抑制剂）作为对抗耐药性的手段。每种多疗法的前景和面临的挑战都从如何有效地在患者中部署这些疗法的角度进行了阐述。我们强调了利用计算方法来预测有效的多种疗法的努力，以及新兴的观点，即特殊应答者可能是更好地理解耐药性的关键。这篇综述强调了在个体化癌症医学时代，多重疗法作为靶向耐药信号网络和实现持久临床反应的有效手段的重要性。
Drug resistance remains one of the greatest challenges facing precision oncology today. Despite the vast array of resistance mechanisms that cancer cells employ to subvert the effects of targeted therapy, a deep understanding of cancer signalling networks has led to the development of novel strategies to tackle resistance both in the first-line and salvage therapy settings. In this review, we provide a brief overview of the major classes of resistance mechanisms to targeted therapy, including signalling reprogramming and tumour evolution; our discussion also focuses on the use of different forms of polytherapies (such as inhibitor combinations, multi-target kinase inhibitors and HSP90 inhibitors) as a means of combating resistance. The promise and challenges facing each of these polytherapies are elaborated with a perspective on how to effectively deploy such therapies in patients. We highlight efforts to harness computational approaches to predict effective polytherapies and the emerging view that exceptional responders may hold the key to better understanding drug resistance. This review underscores the importance of polytherapies as an effective means of targeting resistance signalling networks and achieving durable clinical responses in the era of personalised cancer medicine.