Utilizing targeted cancer therapeutic agents in combination: novel approaches and urgent requirements
Utilizing targeted cancer therapeutic agents in combination: novel approaches and urgent requirements
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DOI：
10.1038/nrd3216
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发表时间：
2010-11-01
影响因子：
120.1
通讯作者：
Doroshow, James H.
中科院分区：
文献类型：
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作者：
Kummar, Shivanni;Chen, Helen X.;Doroshow, James H.
靶向参与肿瘤细胞增殖的特异性分子途径的新治疗剂的快速发展提供了前所未有的机会，以实现比以前传统化疗抗癌剂可能达到的更高程度的生化特异性。然而，这些已建立的化疗药物缺乏特异性，允许相对直接的方法将其用于联合治疗。另一方面，开发一种用于组合新的分子靶向药物的范例要复杂得多。丰富的分子数据使得至少在理论上有可能预测这些因子如何在关键的生长控制网络中相互作用。最初的策略，以检查分子靶向药物组合已产生了少量的成功，在临床上。然而，对于这些组合策略中的大多数，在临床前模型和患者中，尚不清楚组合的药剂是否实际上达到其靶点以诱导生长抑制。在这里，我们认为美国国家癌症研究所（NCI）的初步方法，以评估患者的分子靶向抗癌药物的组合，并提供了几个新的方法，NCI已经开始提高癌症的组合靶向治疗的有效性的描述。
The rapid development of new therapeutic agents that target specific molecular pathways involved in tumour cell proliferation provides an unprecedented opportunity to achieve a much higher degree of biochemical specificity than previously possible with traditional chemotherapeutic anticancer agents. However, the lack of specificity of these established chemotherapeutic drugs allowed a relatively straightforward approach to their use in combination therapies. Developing a paradigm for combining new, molecularly targeted agents, on the other hand, is substantially more complex. The abundance of molecular data makes it possible, at least in theory, to predict how such agents might interact across crucial growth control networks. Initial strategies to examine molecularly targeted agent combinations have produced a small number of successes in the clinic. However, for most of these combination strategies, both in preclinical models and in patients, it is not clear whether the agents being combined actually hit their targets to induce growth inhibition. Here, we consider the initial approach of the US National Cancer Institute (NCI) to the evaluation of combinations of molecularly targeted anticancer agents in patients and provide a description of several new approaches that the NCI has initiated to improve the effectiveness of combination-targeted therapy for cancer.