Taxol® and Camptothecin™
In the mid-1960s, two pioneering scientists at RTI, Dr. Monroe Wall and Dr. Mansukh C. Wani, reported the first of several remarkable discoveries that eventually revolutionized modern cancer research. Their unprecedented achievement produced two compounds instrumental in the fight against cancer---camptothecin and Taxol.
By isolating and elucidating the structure of these novel, bioactive natural products, RTI scientists have improved the lives of cancer patients, unearthed new mechanisms of action for inhibiting cancer cell growth, and established new principles for discovering other bioactive compounds from natural sources.
In June 2000, Drs. Wall and Wani received one of the most prestigious awards for applied research in medicine, the Charles F. Kettering Prize from the General Motors Cancer Research Foundation. The Prize recognizes the most outstanding achievements in cancer treatment and diagnosis. The two researchers have received numerous awards for their medical research and development.
In 1966, Drs. Wall and Wani and their colleagues reported the discovery of a compound they termed camptothecin from the Chinese tree Camptotheca acuminata. Nearly 20 years later, the unique mode of action for this potent cytotoxic compound was found to be the inhibition of an enzyme known as DNA topoisomerase I. Camptothecin traps this enzyme, inhibiting DNA replication and killing the cancer cells.
Presently, first-generation analogs of camptothecin, such as Hycamtin (topotecan) and Camptosar (irinotecan or CPT-11), marketed by GlaxoSmithKline and Pfizer, respectively, are used for the treatment of ovarian and colon cancer.
Perhaps more well known to the public, in 1971 the RTI team reported the structure of Taxol found in the Pacific yew tree, Taxus brevifolia. The unique mode of action for this compound was found to be the stabilization of microtubule assembly, an important step in cell division. Thus, Taxol terminates cancer cell growth. In 1992, Bristol-Myers Squibb received approval to market Taxol for the treatment of refractory ovarian cancer, and subsequently it was approved for the treatment of metastatic breast and lung cancers and Kaposi's sarcoma.
The above achievements represent seminal discoveries for the treatment of cancer. Taxol and compounds derived from camptothecin have been responsible for saving the lives of hundreds of thousands of people afflicted with cancer. Many statistics could be cited in this regard, but one of the more telling relates to the treatment of ovarian cancer: since the inclusion of Taxol in the treatment regimen for this disease, the survival rate has more than doubled.
Furthermore, both Taxol and camptothecin were found to inhibit cancer cell growth via novel mechanisms of action. Prior to their discovery, neither the stabilization of microtubule assembly nor the inhibition of topoisomerase I were known to be effective ways to circumvent the uncontrolled growth of cancer cells. Thus, these compounds have led to new paradigms in the treatment of cancer.
Finally, the RTI team also contributed significantly to the field of natural products chemistry. Both compounds were discovered using the principles of bioactivity-directed fractionation, especially in vitro cytotoxicity as a predictor of in vivo efficacy. This means that simple bioassays can be used to predict whether plant extracts or natural product compounds will have activity in human beings, helping to focus and accelerate research towards new treatments.
Today, these techniques are used routinely in natural product laboratories around the world, including RTI's Natural Products Laboratory, to discover bioactive compounds from plant, marine, and fungal origins.
Taxol (a word coined by RTI's Monroe E. Wall) is a trademark of Bristol-Myers Squibb Co. Camptothecin is a trademark of RTI.