TAXOL: BEFORE AND NOW

Inhibition of cell division

A well know cellular function is that of mitosis; which is the biological function whereby a cells nucleus splits into two identical units. The process is accompanied by cytokinesis where the cell membrane, cytosole and separate nuclei divide into to cells. This complete process is referred to as the”M” phase in the cell cycle theory [1;2] The complete process is supported by a scaffolding type structure called microtubules which provide the framework for cytokinesis and mitosi  [1-3]A mitotic inhibitor is one which interferes with the stability of the microtubules which is of relevance in chemotherapy since unregulated cell division is one the strongest difference between tumor and normal cells [4] This difference can be exploited by a specifically designed inhibitor. Taxol, more commonly called Paclitaxel, is an inhibitor which disrupts the dismantling of the microtubules during cell division, hence cell mitosis cannot occur. Taxol is standard therapy in many forms of cancer including sarcoma [5;6], breast cancer [7-9], NSCLC[10], SCLC, ovarian cancer [11;12] as well as head and neck cancer [13-15].

Taxol: Properties and Availability

Taxol is one of the formulation trade names for Paclitaxel which was developed by the pharmaceutical company Bristol-Myers in the late 1960’s to early 1970’s. Taxol manufacturers use a second trade, Abraxane, to promote a different formulation compared to Taxol. Abrazane contains Paclitaxel bound to protein while taxol consists of a cremophor / ethanol formulation of Paclitaxel. The two different formulations, therefore, have totally different absorption and transport properties as well as use in different disease conditions. The Taxol structure is highly complex consisting of a cyclic carbon chain (17 C) with numerous centers of chirality (11). The enantiomer that demonstrates biological activity is the (-) isomer. Taxol is a formulation trade name with the active drug being paclitaxel, the Taxol Stability in this formulation is reported to be fair, with an expiration date of 2 years if stored at -20°C. Researchers can buy Taxol free base from a variety of Taxol suppliers although Taxol price is dependent on the supplier. The Taxol price of a 100 mg vial can range from $43 up to $2000 researchers while the Taxol cost per patient has been publicly recorded and is approximately £4000 for a 4 cycle course.  Taxol solubility is listed online as 200 mg/ml in DMSO and as 5 mg/ml in Ethanol but these statements refers to the active ingredient paclitaxel. The does exist some confusion in literature about when to use the name Taxol or the name Paclitaxel.

Taxol: Preclinical investigations

The much debated and the controversial molecule Taxol was isolated from a natural source in the early 1960’s. During development the demand for the natural source of taxol increase to the point where significant environmental damage was been done in the name of science. This was resolved when it was realized that the source of Taxol was not the bark of the yew tree but a fungus in the bark, production change them to the closed system of culturing fungus for a Taxol source. During all the political controversy the molecule was investigated for its role on Taxol microtubule stabilization while it was also determined that taxol was active in leukemic murine models and in xenografts of solid tumors [16;17]The Taxol mechanism of action has been theorized to be the stabilization of the polymeric makeup of the microtubule halting disassembly into new cells[18].

Taxol: Clinical Status

Taxol is an approved drug in several different disease groups as a result of a multitude of Taxol clinical trials conducted phase 1, 2 and 3 levels. Taxol / Carboplatin combination is standard therapy for both ovarian, breast and lung cancer, Taxol ovarian cancer treatment is published as being approximately 30% efficient while breast cancer shows a 48% improvement over the previous standard therapy. For Taxol lung cancer statistics indicate that approximately 20-30% of patients responds to treatment and depending on the stage when diagnosed have a 5-50% 5 year survival rate. This may seem low but compared to the previous standard treatment is considered a tremendously move forward.

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