Shanker Manish, Jin Jiankang, Branch Cynthia D, Miyamoto Shinya, Grimm Elizabeth A, Roth Jack A, Ramesh Rajagopal
Department of Thoracic and Cardiovascular Surgery, The University of Texas of MD Anderson Cancer Center, Houston, TX 77030, USA.
J Drug Deliv. 2011;2011:465845. doi: 10.1155/2011/465845. Epub 2011 Jan 24.
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.
癌症是全球主要的健康问题。癌症治疗方面取得的进展提高了某些类型癌症患者的生存率。然而，大多数癌症类型的总体五年生存率并未显著提高。有效进行癌症治疗面临的主要挑战包括肿瘤细胞产生耐药性、非特异性细胞毒性以及化疗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。包括作者所在实验室在内的多个实验室一直在研究用于递送治疗性基因的非病毒制剂，作为一种有效的癌症治疗方式。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，以及他们临床前研究的结果，这些结果促成了一项针对非小细胞肺癌的I期临床试验。他们含有治疗性基因（如肿瘤抑制基因）的纳米载体制剂经静脉给药后可有效控制转移性肿瘤的生长。基于其纳米载体制剂结果的其他I期临床试验已启动或计划用于治疗乳腺癌、卵巢癌、胰腺癌和转移性黑色素瘤，本文将对此进行讨论。
