Alkylating agents

Anti-proliferative
- Bind via alkyl groups to DNA
- Arrest cell cycle in the G1/S phase
Cyclophosphamide, chlorambucil, dacarbazine
Melphalan (used in isolated limb perfusion for melanoma ± sarcoma)
Streptozocin (toxic to beta islet cells)
Mitomycin C = alkylating agent too; DNA cross-linker (derived from Streptomyces)
Platinum based chemotherapy

Anti-metabolites

Interrupts S phase – masquerade as purines/pyrimidines → inhibit DNA synthesis
5-FU (IV) - inhibit Thymidylate synthase therefore decreased production of thymine which is essential in DNA
Capecitabine (oral)
Methotrexate - inhibits dihydrofolate reductase which decrease folate. Folate is required for Thymidylate synthase and therefore it decreases DNA synthesis
Gemcitabine
Azathioprine
6-Mercaptopurine

→ DNA structure not maintained → produced single-strand breaks in DNA & ultimately apoptosis
Top 1 - Irinotecan
Top 2

M-phase - (aka plant alkaloids) – bind tubulin and so impair microtubules in mitotic spindle → cell arrest in metaphase
Vincalcaloids; Vincristine, vinblastine, binblastine - Taxane: Paclitaxel, Docetaxel

Response rates approach 70%
Bevacizumab (Avastin) = antibody to VEGF (vascular endothelial growth factor)
- Action partly thought to be by ‘normalising’ the disorganized vasculature found in tumours → ↑ed delivery of other chemo agents
- Toxicity: thrombosis, bleeding, problematic wound healing, hypertension also proteinuria, headache, fever, rash
- Used in colon CA & breast CA
Cetuximab = antibody to EGFR → cytostatic (through G1 arrest)
- Toxicity: acneaform skin rash (correlates with response), paronychia cracking in up to 20% of patients
Gefitnib = antibody to EGFR
Erlotinib = antibody to EGFR tyrosine kinase
Lapatinib (Tycerb) = antibody to EGFR (inside cell & downstream cascade) and Her-2/neu and Her-1
Trastuzumab (Herceptin) = Ab to Her-2/neu
Imatinib (Gleevac)
(Also Infliximab & Adalimumab for IBD)
Sorafenib = protein kinase inhibitors involved in PDGF, VEGF & cKIT pathways
- Used in HCC & renal cell CA