Cyclophosphamide is an alkylating agent used to treat white blood cell cancers and lymphoma. It works by being metabolized into phosphoramide mustard, which adds alkyl groups to DNA, forming crosslinks between and within DNA strands. This leads to DNA damage and ultimately cell death. The expression of genes coding for enzymes involved in cyclophosphamide metabolism, such as cytochrome P450 and ALDH, can affect how sensitive cancer cells are to the drug.

1. CYCLOPHOSPHAMIDE
Ferdinand F. Fatiga, RMT

2. CYCLOPHOSPHAMIDE
 Used in the treatment of WBC cancers
(AML/ALL) and Lymphoma
 Cell Cycle – Non specific
 Alkylating agent
 Adds Alkyl group (CnH2n+1) to DNA

3. CYCLOPHOSPHAMIDE
 Mechanism of Action
• the main effect of cyclophosphamide is due to
its metabolite Phosphoramide mustard
• Phosphoramide mustard forms DNA crosslinks
between (interstrand crosslinkages) and
within (intrastrand crosslinkages) DNA strands
at guanine N-7 position, this eventually leads
to cell death

5. CYCLOPHOSPHAMIDE Activation


6. CYCLOPHOSPHAMIDE


7. CONCLUSION
Expression of genes that code for
Cytochrome P450 (Oxidase Enzyme) and
ALDH enzymes affects the sensitivity of
Cancer cells to Cyclophosphamide since
these enzymes affect the metabolism of
the prodrug (Cyclophosphamide) to its
active Phosphoramide mustard
metabolite.