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Abstract
Suicide gene therapy is a treatment strategy designed to enhance the efficacy
of drug therapy of cancer by targeting cytotoxic drugs to the tumor but not
normal cells. It involves delivery of enzyme coding gene to tumor cells
where the expressed enzyme can convert a nontoxic prodrug molecule once
entering the cell to toxic drugs leading to apoptosis and cell suicide. The
enzyme-prodrug pairs being explored include HSV-TK/GCV, CD/5-FC,
NTR/CB1954, CYP450/Cyclophosphamide, and CPG2/CMDA. Enzyme
coding genes are cloned into plasmid or packaged into viral vectors that
facilitate gene transfer into target cells. Following prodrug administration,
cytotoxic effects are seen in all tumor cells through a mechanism of
bystander effect. The focus of this thesis is to provide a brief introduction on
cancer biology, and the treatment strategies currently available for cancer
therapy. A major emphasis will be placed on the approaches of suicide gene
therapy against cancer with detailed rationale of each approach, current
progress and future perspectives for their clinical applications.
of drug therapy of cancer by targeting cytotoxic drugs to the tumor but not
normal cells. It involves delivery of enzyme coding gene to tumor cells
where the expressed enzyme can convert a nontoxic prodrug molecule once
entering the cell to toxic drugs leading to apoptosis and cell suicide. The
enzyme-prodrug pairs being explored include HSV-TK/GCV, CD/5-FC,
NTR/CB1954, CYP450/Cyclophosphamide, and CPG2/CMDA. Enzyme
coding genes are cloned into plasmid or packaged into viral vectors that
facilitate gene transfer into target cells. Following prodrug administration,
cytotoxic effects are seen in all tumor cells through a mechanism of
bystander effect. The focus of this thesis is to provide a brief introduction on
cancer biology, and the treatment strategies currently available for cancer
therapy. A major emphasis will be placed on the approaches of suicide gene
therapy against cancer with detailed rationale of each approach, current
progress and future perspectives for their clinical applications.