ErbB2 signaling at the crossing between heart failure and cancer.
ErbB2 signaling at the crossing between heart failure and cancer.
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DOI：
10.1007/s00395-016-0576-z
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发表时间：
2016-11
影响因子：
9.5
通讯作者：
De Keulenaer GW
中科院分区：
文献类型：
--
作者：
Vermeulen Z;Segers VF;De Keulenaer GW
ErbB 2（或HER-2）在肿瘤生长和心脏生理适应性反应中的双重作用使ErbB 2处于癌症和慢性心力衰竭之间的交叉点。因此，癌症的ErbB 2靶向抑制治疗可能导致心室功能障碍，并且用于心力衰竭治疗的ErbB 2的激活可能诱导恶性肿瘤。然而，导致肿瘤和心脏细胞中ErbB 2活化的分子过程彼此根本不同。因此，设计特异性靶向生理或恶性ErbB 2信号传导的药物，在心力衰竭中激活ErbB 2信号传导而不增加癌症风险，以及在癌症中抑制ErbB 2信号传导而不增加心力衰竭风险，必须是可行的。在这篇综述中，我们介绍了ErbB 2在生理条件下和肿瘤细胞中的调节方式，以及这些知识如何转化为智能药物设计。这导致新一代药物以独特的方式干扰ErbB 2，为特定的临床目标量身定制。这些令人兴奋的发展在癌症和心力衰竭之间的交叉是临床医生，生理学家，药理学家和分子生物学家之间的跨学科合作的一个优雅的例子。
The dual role of ErbB2 (or HER-2) in tumor growth and in physiological adaptive reactions of the heart positions ErbB2 at the intersection between cancer and chronic heart failure. Accordingly, ErbB2-targeted inhibitory therapy of cancer may lead to ventricular dysfunction, and activation of ErbB2 for heart failure therapy may induce malignancy. The molecular processes leading to the activation of ErbB2 in tumors and cardiac cells are, however, fundamentally different from each other. Thus, it must be feasible to design drugs that specifically target either physiological or malignant ErbB2 signaling, to activate ErbB2 signaling in heart failure with no increased risk for cancer, and to inhibit ErbB2 signaling in cancer with no increased risk for heart failure. In this review, we present a state-of-the-art on how ErbB2 is regulated in physiological conditions and in tumor cells and how this knowledge translates into smart drug design. This leads to a new generation of drugs interfering with ErbB2 in a unique way tailored for a specific clinical goal. These exciting developments at the crossing between cancer and heart failure are an elegant example of interdisciplinary collaborations between clinicians, physiologists, pharmacologists, and molecular biologists.
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