title: Tumor suppressor gene-based nanotherapy: from test tube to the clinic.
abstract: 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.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas of MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Shanker
authors.forename: Jiankang
authors.initials: J
authors.lastname: Jin
authors.forename: Cynthia D
authors.initials: CD
authors.lastname: Branch
authors.forename: Shinya
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Grimm
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Ramesh