|Taxanes||Mechanism of Action|
|Paclitaxel, docetaxel (nab-paclitaxel)||Stabilizes microtubules and causes mitotic arrest and apoptosis|
- 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.
- The inhibitor of apoptosis protein survivin promotes progression through G2/M and interferes with induction of cell death.
- ER increases the expression of survivin and
- BRCA1 blocks ER function thereby decreasing survivin levels.
- TLE3 blocks activity of the transcriptional regulator, FOXA1, which controls expression of genes such as RelB, that enable cell survival.
- PGP effluxes taxanes thereby decreasing their intra-cellular concentrations.
- SPARC binds albumin in nab-paclitaxel to locally increase the paclitaxel levels.
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Green squares, sensitivity markers. Red squares, resistance markers