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Tumor Suppressor Gene-Based Nanotherapy: From Test Tube to the Clinic

机译:基于肿瘤抑制基因的纳米疗法:从试管到诊所

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Cancer is a major health problem in the world. Advances made in cancer therapy have improved the survival of patients in certain types of cancer. However, the overall five-year survival has not significantly improved in the majority of cancer types. Major challenges encountered in having effective cancer therapy are development of drug resistance by the tumor cells, nonspecific cytotoxicity, and inability to affect metastatic tumors by the chemodrugs. Overcoming these challenges requires development and testing of novel therapies. One attractive cancer therapeutic approach is cancer gene therapy. Several laboratories including the authors' laboratory have been investigating nonviral formulations for delivering therapeutic genes as a mode for effective cancer therapy. In this paper the authors will summarize their experience in the development and testing of a cationic lipid-based nanocarrier formulation and the results from their preclinical studies leading to a Phase I clinical trial for nonsmall cell lung cancer. Their nanocarrier formulation containing therapeutic genes such as tumor suppressor genes when administered intravenously effectively controls metastatic tumor growth. Additional Phase I clinical trials based on the results of their nanocarrier formulation have been initiated or proposed for treatment of cancer of the breast, ovary, pancreas, and metastatic melanoma, and will be discussed.
机译:癌症是世界上的主要健康问题。癌症治疗方面的进展提高了某些类型癌症患者的生存率。但是,在大多数癌症类型中,总体五年生存期并未显着改善。在有效的癌症治疗中遇到的主要挑战是肿瘤细胞的耐药性发展,非特异性细胞毒性以及化学药物无法影响转移性肿瘤。克服这些挑战需要开发和测试新型疗法。一种有吸引力的癌症治疗方法是癌症基因治疗。包括作者实验室在内的几个实验室一直在研究用于递送治疗基因的非病毒制剂,作为有效癌症治疗的一种方式。在本文中,作者将总结他们在开发和测试基于阳离子脂质的纳米载体制剂方面的经验,以及他们的临床前研究结果,这些结果导致了针对非小细胞肺癌的I期临床试验。当静脉内施用时,它们的包含治疗基因例如肿瘤抑制基因的纳米载体制剂有效地控制了转移性肿瘤的生长。基于其纳米载体制剂结果的其他I期临床试验已经启动或提议用于治疗乳腺癌,卵巢癌,胰腺癌和转移性黑色素瘤,并将进行讨论。

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