Taxanes versus vinca alkaloids: microtubule effects
Taxanes lock microtubules (hollow protein tubes, the cell's internal scaffolding) so they cannot be broken down, while vinca alkaloids (cancer drugs) stop them being built.
Remember
Taxanes stabilise microtubules and stop them depolymerising (breaking down into subunits), whereas vinca alkaloids block polymerisation (adding subunits). Both arrest cells in M phase, the point in the cell cycle at which a cell divides.
Memory aid
vinca alkaloids stop the scaffold going up, while taxanes stop it coming down
Picture the spindle as a scaffold: vinca alkaloids stop it being put up, whereas taxanes stop it being taken down.
Microtubules are hollow protein tubes. In a dividing cell they make up the mitotic spindle, a scaffold that drags the copied chromosomes into the two daughter cells. To work, the spindle has to be assembled and taken apart again and again. Adding protein subunits is called polymerisation, and removing them is depolymerisation.
Taxanes, such as paclitaxel and docetaxel, bind microtubules and stabilise them, so they cannot be broken down. The spindle becomes rigid and cannot reorganise. The cell is held, or arrested, in M phase, the point in the cell cycle at which a cell divides, and the cells die.
Vinca alkaloids, such as vincristine and vinblastine, act on the same structures but in the opposite direction. They inhibit polymerisation, so the spindle is never built, and cells are again arrested in M phase. Both groups are spindle poisons, meaning drugs that disrupt the mitotic spindle.
Peripheral neuropathy, which is damage to the nerves outside the brain and spinal cord, is the signature toxicity of vincristine and a notable toxicity of the taxanes. Vincristine is also fatal if it is given intrathecally (into the fluid around the spinal cord) instead of into a vein.
Key facts
- Taxanes
- paclitaxel and docetaxel stabilise microtubules, which prevents their depolymerisation.
- Vinca alkaloids
- vincristine and vinblastine inhibit microtubule polymerisation, so a spindle is never built.
- M phase
- both groups arrest cells in it, so both are M-phase specific (they act on cells during M phase).
- Taxane toxicities
- peripheral neuropathy, neutropenia (a low count of neutrophils, the white cells that fight bacteria) and hypersensitivity, the last linked to cremophor, the solvent in which paclitaxel is dissolved.
- Vincristine
- its signature toxicity is peripheral neuropathy, and it is fatal if given intrathecally instead of intravenously.
Exam traps
- Vinblastine arrests cells in M phase just as paclitaxel does, but it is a vinca alkaloid that inhibits microtubule polymerisation, so it does not prevent depolymerisation.
- Stabilising microtubules to prevent their breakdown is the taxane mechanism, not that of vincristine, which blocks microtubule assembly. The classic confusion arises because taxanes also act on microtubules and can cause neuropathy.
- Peripheral neuropathy alone does not point to a microtubule drug, because cisplatin can cause it too, and cisplatin cross-links DNA at any point in the cell cycle rather than stabilising microtubules.
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