Pool Martin, de Boer H Rudolf, Hooge Marjolijn N Lub-de, van Vugt Marcel A T M, de Vries Elisabeth G E
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Theranostics. 2017 May 27;7(7):2111-2133. doi: 10.7150/thno.17934. eCollection 2017.
Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance.
癌症是一个在全球范围内日益严重的问题。癌症患者的死因通常是对治疗有抗性的转移性疾病。许多针对“致癌驱动”通路的分子靶向抗癌药物已经研发出来。然而,这些治疗通常仅在经过适当选择的患者中有效。通过对获得性突变或分子重排施加选择性压力而产生的对分子靶向药物的抗性,可能会阻碍其疗效。本综述总结了分子成像技术如何有可能促进靶向药物的最佳应用。在(临床前)研究中,以人类表皮生长因子受体(HER)家族作为模型,我们阐述了如何利用分子成像来表征全身靶点表达,以及监测药物疗效和肿瘤抗性的出现。我们还进一步讨论了一个整合组学发现平台如何能够指导“效应传感器”——新的分子成像靶点——的选择,这些靶点是指示治疗效果或抗性的动态标志物。