11 Dec 2011

Pacific Yew

In keeping with a holiday theme, I thought we would look into one of the most important drugs in all of the ovarian cancer treatment arsenal - taxol - a drug originally derived from an evergreen tree.
Taxol has had a very interesting and lengthy history starting in the 1950's with an edict from the National Cancer Institute's Natural Plants Division to screen about 1,000 plants per year.  Botanists were sent all across the USA to collect specimens and in this case, the bark of the Pacific Yew tree - taxus brevifolia.  Fast forward to 1964 when taxus was discovered to be cytotoxic (cause cell death).  It took until 1977 for the extract to be recommended for in vitro trials and by 1980, the NCI forecasted a requirement for about 20,000 lbs of bark.
Human trials began in 1984.  In 1988, a Phase II clinical trial produced a remarkable 30% response rate in ovarian cancer patients causing the Natural Plants Division to realise that it would take the destruction of more that 360,000 yew trees to meet the demand that year for this remarkable drug.  Various companies were charged with the task of mass production of the trees.  Attempts were made to extract the drug from the needles but the results were too inconsistent.

As with any blockbuster discovery, word spread quickly and the race was on to synthesise taxol.  Ultimately, in 1994 a combination of laboratories in the US, Canada and Germany were able to produce a formula which is now licenced to Bristol Myers Squibb for mass production.

Wikipedia has this interesting addendum to the story:

"Recently a group of Italian researchers in the Department of Translational Oncology, National Institute for Cancer Research, IST, Genova with the collaboration of the University of Genova, Italy, has confirmed the presence of taxanes in the shells and leaves of hazel plants, including paclitaxel, 10-deacetylbaccatin III, baccatin III, paclitaxel C, and 7-epipaclitaxel. The finding of these compounds in shells, which are considered discarded material and are mass produced by many food industries, is of interest for the future availability of paclitaxel (Taxol)."

Taxol combined with carboplatin is the first-line treatment today for ovarian cancer patients.  For various reasons, some patients - including myself, are allergic to this drug.  Patients can be "desensitized" to it - as I was - and/or offered new derivatives which have been developed recently.

It's mind-boggling to absorb the dates in the development of this drug  - 1964 to 1994 - thirty years from the petrie dish  to mass production of something as vital as this.  I can only imagine the women in the '60's clambering to get their names on the list of  trial participants... not much different from today.

The Pacific Yew has been saved from extinction by the genius of our scientific community but more significantly, this humble tree has directly saved and prolonged the lives of many ovarian cancer patients.

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