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Recombinant expression of cytochrome P450-2D6 and its application in tamoxifen metabolism

Magister Scientiae - MSc (Biotechnology) / Breast cancer is regarded as the most common form of cancer in women and it comprises of
approximately 23 % of female cancers, while affecting women at any age range. For
oestrogen receptor positive patients, tamoxifen is used as a prescribed medication for breast
cancer therapy. However, tamoxifen in its natural form is not active to achieve the required
treatment and prevention of breast cells proliferation. Since tamoxifen is a prodrug, it need to
be converted into its active form, endoxifen, for which it is achieved by the action of the
cytochrome P450 enzymes. Cytochrome P450 2D6 (CYP2D6) is a member of cytochrome
P450 enzymes for which are superfamily of heme enzymes characterised by their ability to
catalyse the oxidative reactions of compounds, including the pathway of tamoxifen
metabolism. However, due to polymorphism that lead to inactive phenotypes of CYP2D6 in
this gene, there is a challenge of diagnosing if a patient can metabolise tamoxifen or not. The
current diagnostic tool, Amplichip CYP450, for CYP2D6 is based on genotypes, and it lead
to uncertainness as to whether the presence of functionalCYP2D6 alleles of CYP2D6 may
lead to coding of active protein, thus leading to wrong treatment measures and overdose of
tamoxifen. Electrochemical techniques have provided reliable, simple, quick, and sensitive
methods for the determination of drug metabolism by enzymes. Therefore, it is important to
develop a CYP2D6 phenotype-based sensor to detect and tell whether a particular individual
can metabolise the drug or not.

Identiferoai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uwc/oai:etd.uwc.ac.za:11394/6420
Date January 2018
CreatorsEdwin, Munyai Vukosi
ContributorsMulaudzi-Masuku, Takalani
PublisherUniversity of the Western Cape
Source SetsSouth African National ETD Portal
LanguageEnglish
Detected LanguageEnglish
RightsUniversity of the Western Cape

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