1 Taxane
Taxol (general name paclitaxel) is the first microtubule-stabilizing
drug of taxane family isolated from the yew root. In 1967, Mansukh Wani
and Monroe Wall had isolated and identified the active ingredient from
the bark of T. brevifolia and named it taxol, basing on its
species of origin and the presence of hydroxyl groups [10]. Taxol
enters phase I clinical trials in 1894 and phase II clinical trials in
1895. In the United States, the Phase III clinical trial was completed
in 7 years from 1983 and was approved by the FDA in 1992[11]. Taxol
has been obtained by chemical semi-synthesis, total chemical synthesis,
tissue and cell culture, microbial fermentation and biosynthesis. In
1995, docetaxel, the second member of the family was approved for
medical use. Due to the poor water-solubility of paclitaxel before,
solvent-increasing polyoxyethylene castor oil and anhydrous ethanol will
be added when it is used [12]. As the solvent itself will cause
severe allergic reactions, there were various limitations to clinical
use.
Advances requires to be made because of various restrictions mentioned
above. Currently, paclitaxel family includes traditional paclitaxel,
paclitaxel liposome, paclitaxel nanoparticle albumin bound
(NAB)(Abraxane) and docetaxel (Taxotere). Unlike other
microtubule-stabilizing anticancer drugs which prevent the assembly of
tubulin into microtubules, it is a microtubule stabilizer
(anticontractile agent) and a mitotic inhibitor (antiproliferative
agent) [10]. Paclitaxel promotes the assembly of tubulin to
microtubules and prevents the dissociation of microtubules as well as
blocks cell cycle progression, prevents mitosis, and inhibits the growth
of cancer cells [11]. Thus, paclitaxel has become a widely accepted
chemotherapeutic drug in the treatment of ovarian cancer, breast cancer,
non-small cell lung cancer and a variety of other malignant solid tumors
[13].