Chemo and radiotherapy

• Damages DNA of cancer cells as it divides (mitosis)
• Cell recognises it is damaged beyond repair and dies by apoptosis
• Often involves p53; mutations of p53 make it more difficult to treat with chemo and radiotherapy

Cell cycle specific agents

General characteristics

• Tumour specific (relatively)
• Duration of exposure more important than dose

Antimetabolites

• Impair nucleotide synthesis/incorporation
• Methotrexate inhibits dihydrofolate reductase (impacts folate metabolism)
• 6-mercaptopurine, cytosine arabinoside, fludarabine - incorporated into DNA
• Hydroxyurea - impaired deoxynucleotide synthesis (ribonucleotide reductase)

Mitotic spindle inhibitors

General characteristics

• Non-tumour specific - damage normal stem cells
• Cumulative dose more important than duration

Examples

• Plant derivatives - vinca alkaloids (vincristine/vinblastine), taxotere (taxol)
• Alkylating agents e.g. chlorambucil/melphalan - bind covalently to bases of DNA, produces DNA strand breaks by free radical production