Paclitaxel and Its Evolving Role in the Management of Ovarian Cancer

Figure 3

Mechanism of action of paclitaxel. Paclitaxel targets microtubules. At high concentration, PTX causes mitotic arrest at G2/M phase whereas at low concentration, apoptosis is induced at G0 and G1/S phase either via Raf-1 kinase activation or p53/p21 depending on the dose concentration. Even at lower dose but with exposure beyond 24 hours, paclitaxel can cause mitotic arrest. Paclitaxel also activates multiple signaling pathway to exert proapoptotic activity as well as immunomodulatory effect. Paclitaxel also develops resistance via these signaling pathways. PTX: Paclitaxel, TLR4: Toll-like receptor 4, G0: resting phase, G1; cells enlarge and make new protein, S phase: DNA replication, G2: preparation for division, M phase: cell division/mitosis, Raf-1: Raf kinase family, MEK/MAPK: mitogen activated protein kinase, IRAK: IL-1 receptor associated kinase, TRAF: TNFR associated factor, NF-κB: nuclear factor kappa B, TRIF/TRAM: TIR-domain-containing adapter-inducing interferon-β, TKR: tyrosine kinase receptor, VEGFR: vascular endothelial growth receptor, PI3K: phosphoinositide 3-kinase, JAK: janus kinase, STAT: signal transducer and activator of transcription factor.