Braun Klaus, Wiessler Manfred, Ehemann Volker, Pipkorn Ruediger, Spring Herbert, Debus Juergen, Didinger Bernd, Koch Mario, Muller Gabriele, Waldeck Waldemar
German Cancer Research Center, Dept of Imaging and Radiooncology, Im Neuenheimer Feld 280, Heidelberg, Germany.
Drug Des Devel Ther. 2009 Feb 6;2:289-301. doi: 10.2147/dddt.s3572.
Recurrent glioblastoma multiforme (GBM), insensitive against most therapeutic interventions, has low response and survival rates. Temozolomide (TMZ) was approved for second-line therapy of recurrent anaplastic astrocytoma. However, TMZ therapy in GBM patients reveals properties such as reduced tolerability and inauspicious hemogram. The solution addressed here concerning GBM therapy consolidates and uses the potential of organic and peptide chemistry with molecular medicine. We enhanced the pharmacologic potency with simultaneous reduction of unwanted adverse reactions of the highly efficient chemotherapeutic TMZ. The TMZ connection to transporter molecules (TMZ-BioShuttle) was investigated, resulting in a much higher pharmacological effect in glioma cell lines and also with reduced dose rate. From this result we can conclude that a suitable chemistry could realize the ligation of pharmacologically active, but sensitive and highly unstable pharmaceutical ingredients without functional deprivation. The TMZ-BioShuttle dramatically enhanced the potential of TMZ for the treatment of brain tumors and is an attractive drug for combination chemotherapy.
复发性多形性胶质母细胞瘤（GBM）对大多数治疗干预不敏感，缓解率和生存率较低。替莫唑胺（TMZ）被批准用于复发性间变性星形细胞瘤的二线治疗。然而，GBM患者的TMZ治疗显示出耐受性降低和血常规不良等特性。本文针对GBM治疗提出的解决方案整合并利用了有机化学、肽化学与分子医学的潜力。我们在提高高效化疗药物TMZ药效的同时，减少了其不良副作用。研究了TMZ与转运分子的连接（TMZ-生物穿梭体），结果显示在胶质瘤细胞系中具有更高的药理作用，且给药剂量率降低。由此结果我们可以得出结论，合适的化学方法可以实现药理活性高但敏感且高度不稳定的药物成分的连接，同时不丧失其功能。TMZ-生物穿梭体显著增强了TMZ治疗脑肿瘤的潜力，是联合化疗中一种有吸引力的药物。
