Cytochrome P450 isozymes (CYPs) from the CYP1 and CYP2 families located primarily in extra-hepatic tissues
represent ideal candidates for chemotherapeutic drug development because: 1.) They are usually involved in the metabolism
of endogenous substrates that are important for cell homeostasis and growth 2.) The over-expression of certain
CYPs has been reported in various malignancies 3.) There has been much clinical success with inhibitors of CYPs involved
in hormone synthesis. The most ideal candidates for chemotherapeutic drug development will be discussed in
terms of their biological importance and relevant substrates. This review will focus on: 1.) CYP1A1 and CYP1B1 from
the CYP1 family because of the dual role these enzymes play in the bioactivation of known carcinogens and endogenous
compounds. 2.) The targeting of CYPs in hypoxic environments as a therapeutic strategy. 3.) CYP2J2 and its role in the
metabolism of arachidonic acid to epoxyeicosatrienoic acids and angiogenesis will also be examined. While much progress
has been made towards understanding the role of CYPs in extrahepatic tissue, future studies focused on the development
of selective inhibitors coupled with appropriate delivery systems that would target the tumor micro-environments
could lead to significant advancement in chemotherapeutic strategies.
Keywords: Angiogenesis, carcinogenesis, chemotherapeutic, cytochrome P450, hypoxia, pharmacogenetics.
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