Taxanes Mechanism of Action
Paclitaxel, docetaxel (nab-paclitaxel) Stabilizes microtubules and causes mitotic arrest and apoptosis
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  1. Taxanes bind to and polymerize bII-tubulins, resulting in microtubule stabilization, arrest in the G2/M phase of the cell cycle, and cell death. Paclitaxel and docetaxel are inactive in cells with TUBB3 microtubules.
  2. The inhibitor of apoptosis protein survivin promotes progression through G2/M and interferes with induction of cell death.
  3. ER increases the expression of survivin and
  4. BRCA1 blocks ER function thereby decreasing survivin levels.
  5. TLE3 blocks activity of the transcriptional regulator, FOXA1, which controls expression of genes such as RelB, that enable cell survival.
  6. PGP effluxes taxanes thereby decreasing their intra-cellular concentrations.
  7. SPARC binds albumin in nab-paclitaxel to locally increase the paclitaxel levels.

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Green squares, sensitivity markers. Red squares, resistance markers