Category: catabolism
Traditional cytotoxic chemotherapy delivers DNA-damaging insults that proliferating cells (cancer cells, plus bone marrow + GI + hair follicle) cannot repair in time. Mechanisms: (1) DNA cross-linking — cisplatin/carboplatin form Pt-DNA adducts, cyclophosphamide forges interstrand alkyl bridges; (2) Topoisomerase poisoning — doxorubicin traps Top2-DNA complexes; (3) Microtubule disruption — paclitaxel stabilizes microtubules → arrests mitosis at metaphase; (4) Antimetabolites — 5-FU is a thymidylate synthase inhibitor (block dTMP synthesis), methotrexate is DHFR inhibitor (broader folate-cycle block — purine + pyrimidine + amino-acid synthesis). Immune-modulating offshoots: mycophenolate (IMPDH inhibitor → de novo purine synthesis block, T/B cell selective); azathioprine (6-MP prodrug, thiopurine → DNA incorporation + de novo purine block).