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腾讯登录Ang Chem Int Ed：降低现代癌症疗法严重副作用的新型策略
| 导读 | 近日，刊登在国际杂志Angewandte Chemie International Edition上一篇研究论文中，来自维也纳大学的研究人员通过研究开发出了一种新型的抑制剂，其可以和钴(III)形成化合物进行联合作用，这种化合物可以使得原始的药物失活，而在正常的生理状况下该化合物并没有活性。 |
现代癌症领域面临的最大的两个问题就是严重的副作用和癌症抗性的产生，即使是最新的疗法，高度靶向性的药物比如酪氨酸激酶抑制剂塔西法或舒尼替尼，其仍然会被一些问题所影响，以至于最终癌症疗法被终止；酪氨酸激酶抑制剂的疗法是基于对癌细胞中过度表达的蛋白进行靶向性抑制，然而临床上常会引发患者出现严重的副作用，因此目前研究人员急需一种新型策略来帮助开发可以选择性靶向作用恶性肿瘤的新型药物。
长期以来研究者都试图去开发一种改善型的酪氨酸激酶抑制剂，使其仅仅可以对恶性细胞进行靶向作用；近日，刊登在国际杂志Angewandte Chemie International Edition上一篇研究论文中，来自维也纳大学的研究人员通过研究开发出了一种新型的抑制剂，其可以和钴(III)形成化合物进行联合作用，这种化合物可以使得原始的药物失活，而在正常的生理状况下该化合物并没有活性。在肿瘤细胞存在的情况下，由于肿瘤细胞的快速增殖，通常会产生无氧环境，此时失活的钴(III)化合物会削减形成钴(II)从而释放活性药物，利用这种新型途径，研究人员在活体细胞和肿瘤组织中揭示了该新型化合物对肿瘤的选择性靶向效应。
研究者表示，这种新型化合物的开发技术已经申请了专利，未来也将进行临床研究；目前并没有一种非常完美的策略可以降低酪氨酸激酶抑制剂所引发的机体副作用，而研究人员希望将来可以开发出一种方法有效改善患者对疗法的耐受性，并且使得疗法为患者带来实质性的治疗帮助。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：
Tumor-Targeting of EGFR Inhibitors by Hypoxia-Mediated Activation†
Angewandte Chemie International Edition DOI: 10.1002/anie.201403936
M. Sc. Claudia Karnthaler-Benbakka1,‡, M. Sc. Diana Groza2,‡, Mag. Kushtrim Kryeziu2, Dr. Verena Pichler1, Dipl.-Ing. Alexander Roller1, Prof. Dr. Walter Berger2,3, Dr. Petra Heffeter2,3,* andDr. Christian R. Kowol1,3,*
The development of receptor tyrosine-kinase inhibitors (TKIs) was a major step forward in cancer treatment. However, the therapy with TKIs is limited by strong side effects and drug resistance. The aim of this study was the design of novel epidermal growth factor receptor (EGFR) inhibitors that are specifically activated in malignant tissue. Thus, a CoIII-based prodrug strategy for the targeted release of an EGFR inhibitor triggered by hypoxia in the solid tumor was used. New inhibitors with chelating moieties were prepared and tested for their EGFR-inhibitory potential. The most promising candidate was coupled to CoIII and the biological activity tested in cell culture. Indeed, hypoxic activation and subsequent EGFR inhibition was proven. Finally, the compound was tested in vivo, also revealing potent anticancer activity.
Angewandte Chemie International Edition DOI: 10.1002/anie.201403936
M. Sc. Claudia Karnthaler-Benbakka1,‡, M. Sc. Diana Groza2,‡, Mag. Kushtrim Kryeziu2, Dr. Verena Pichler1, Dipl.-Ing. Alexander Roller1, Prof. Dr. Walter Berger2,3, Dr. Petra Heffeter2,3,* andDr. Christian R. Kowol1,3,*
The development of receptor tyrosine-kinase inhibitors (TKIs) was a major step forward in cancer treatment. However, the therapy with TKIs is limited by strong side effects and drug resistance. The aim of this study was the design of novel epidermal growth factor receptor (EGFR) inhibitors that are specifically activated in malignant tissue. Thus, a CoIII-based prodrug strategy for the targeted release of an EGFR inhibitor triggered by hypoxia in the solid tumor was used. New inhibitors with chelating moieties were prepared and tested for their EGFR-inhibitory potential. The most promising candidate was coupled to CoIII and the biological activity tested in cell culture. Indeed, hypoxic activation and subsequent EGFR inhibition was proven. Finally, the compound was tested in vivo, also revealing potent anticancer activity.
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