Paclitaxel, commonly known as Taxol, is a drug used for the treatment of cancer like the ovarian and breast cancer.
Taxol acts by disrupting microtubule structure, ultimately resulting in cancer cell death.
The drug was discovered between the 1960s and 1980s, as a result of an extensive plant screening during which as many as 15.000 plant extracts were evaluated for anticancer activity.
This lead to finding that the extract from Taxus Brevifolia’s bark was cytotoxic. In 1967 was isolated the part of the bark and named Taxol and in 1971 its structure was published.
Initially, Taxol’s utility was met with skepticism since the drug was insoluble in water and had to be mixed with polyethoxylated castor oil, which can cause anaphylactic reactions.
Regardless, scientists kept working on Taxol finding it to be effective against some mouse tumor models. After a number of clinical trials, however, the availability of Taxol became limited due to the slow growth of parent plant T.Brevifolia.
Despite its scarcity, a clinical study on ovarian cancer showed that 30% of patients with advanced disease were responding to Taxol treatment.
However, bottlenecks in drug production remained a persisting problem, so the race started for developing the drug by chemical synthesis.
At this point National Cancer Institute (NCI) made the decision to license out Taxol to the pharmaceutical company Bristol-Myers Squibb (BMS) in 1991 for commercialization.
How does it work?
Paclitaxel treatment freezes cells at the mitotic stage, when there is a small number of unattached kinetochores.
Taxol induces the mitotic arrest due to the activation of mitotic checkpoint as a result it delays the separation of the chromosomes.
These enter in mitosis like sister chromatids until each pair is attached by mitotic spindle.
As result, each daughter cell will have one copy of chromatid. The chromatids are connected to the microtubules through their kinetochores; in case of unattached kinetochores there is a signal for the transduction cascade for the delay of mitotic progression.
