Classical Anticancer Agents Overview

Cancer Chemotherapy Revision Sheet

1. 📌 Essentials

• Classical anticancer agents target specific phases of the cell cycle, mainly S-phase.
• Main drug classes: antimetabolites, alkylating agents, cytotoxic antibiotics, plant alkaloids/microtubule inhibitors.
• Folate antagonists (e.g., methotrexate) inhibit DHFR, blocking purine and thymidylate synthesis.
• Alkylating agents form covalent DNA crosslinks, causing DNA damage and apoptosis.
• Resistance mechanisms include decreased drug uptake, increased DNA repair, and P-glycoprotein-mediated efflux.
• Tumor growth stages: A (dividing), B (resting but capable), C (non-dividing).
• Topoisomerases manage DNA supercoiling; targeted by specific antibiotics.
• Microtubule inhibitors arrest mitosis at metaphase.
• P-glycoprotein (P-gp) is a key efflux transporter mediating multidrug resistance.
• Chemotherapy's limited selectivity causes collateral damage to normal proliferating cells.

2. 🧩 Key Structures & Components

• Folate pathway — essential for nucleotide synthesis.
• DNA crosslinks — caused by alkylating agents.
• Topoisomerases I & II — enzymes managing DNA supercoiling.
• Microtubules — composed of tubulin, critical for mitosis.
• P-glycoprotein (P-gp) — efflux pump reducing intracellular drug levels.
• DNA — primary target for alkylating agents and antibiotics.
• Cell cycle phases — S-phase (DNA synthesis), M-phase (mitosis).

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