Alkylating agents and antimetabolites
The two oldest chemotherapy families: alkylators (cyclophosphamide, temozolomide, melphalan) glue DNA strands together so cells cannot copy them; antimetabolites (5-FU, capecitabine, methotrexate, gemcitabine) are fake building blocks that jam DNA synthesis.
Alkylating agents descend from mustard gas (nitrogen mustard, 1946): cyclophosphamide anchors lymphoma and breast regimens and lymphodepletion, temozolomide treats glioblastoma, melphalan and busulfan are transplant conditioning, and platinum drugs act similarly. Antimetabolites include fluoropyrimidines (5-FU, capecitabine, S-1) in gastrointestinal and breast cancer, methotrexate and cytarabine in leukaemia, gemcitabine in pancreatic and bladder cancer and pemetrexed in non-squamous lung cancer. Alkylators are mutagenic and cause secondary leukaemia and infertility; antimetabolite toxicity depends on enzymes such as DPD (5-FU) and can be reduced by pre-treatment genotyping.
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