News from Illinois CancerCare

The Origins of Chemotherapy

By: Michele Woods, Oncology Pharmacy Clinical Specialist

I would like to share with you some of the history behind the development of cancer medications. I think you will be surprised to learn where the chemotherapies we use today came from. Our story begins with victims of nerve gas exposure during WWI. It was observed that in addition to reddening and blistering the skin, blistering the lining of the lungs, and eventually rendering the victim blind, mustard gas also attacked the white blood cells and lymphatic tissue. By the early 1940s, two pharmacologists named Goodman and Gilman were doing experiments that involved administering a nitrogen mustard to mice and then to a human with lymphoma. Drug products currently in use include mechlorethamine, cyclophosphamide, chlorambucil, and melphalan. Surprisingly, a new chemotherapy agent derived from the nitrogen mustard chemical structure was just approved by the FDA this year. Although the first chemotherapy agents were poisons – and that is certainly the association that many of us have, not all cancer treatments began as toxic chemicals. A surprising number of chemotherapy agents used to treat cancer have origins as natural products. In fact, around twenty-five percent of all prescription drugs in the United States are derived from plants. The potential for discovering medicines is often cited as an argument for international cooperation in preserving tropical forests. Because the useful products that are found can often be extracted profitably from the plants and animals of the rainforest, bio-prospecting can also function as a means for supporting conservation efforts. Bio-prospecting may sound like the new gold rush, and in a way, it may be. “Panning” for new drugs can work in either of two ways. Some researchers spend time discussing the plants used by local healers, and then investigating those plants to see how they produce their effects. Other researchers, working on the assumption that surprises may be lurking under every leaf, collect samples of as many plants as possible and test each one for activity against hundreds of diseases. Here is an example of how the first method of bio-prospecting was used to advance cancer treatment. The periwinkle plant has historically been used to treat a wide assortment of diseases. In India, juice from the leaves was used to treat wasp stings. In Hawaii, it was boiled to make a poultice to stop bleeding. In China, it was used as an astringent, diuretic, and cough remedy. In Central and South America, it was used as a homemade cold remedy to ease lung congestion, inflammation, and sore throats. Throughout the Caribbean, an extract from the flowers was used to make a solution to treat eye irritation and infections. It also had a reputation as a magic plant; Europeans thought it could ward off evil spirits, and the French referred to it as “violet of the sorcerers.” It is easy to see why ethnobotanists selected the periwinkle for further study. In the laboratory, bench scientists were able isolate and determine the anticancer activity of the vinca alkaloids from the periwinkle plant. Vinca alkaloid chemotherapies include: Vinblastine, vincristine, vindesine, and vinorelbine. Drugs to fight cancer have also been developed via the second method of bioprospecting. Although the ethnobotanical records have shown that some of the medicinal properties of the Pacific yew have been known for centuries, it wasn’t well studied until 1966, when it was included in a massive screening of 35,000 species by the United States National Cancer Institute. The bright red fruits of yews are called arils and each cups a single seed. The arils, which are moderately sweet, are the only parts of the plant that do not contain poisonous alkaloids called taxanes. The seeds are deadly, so it is not recommended that people eat the arils. Monroe Wall, a chemist from North Carolina, extracted paclitaxel from the bark of Pacific yew and identified it as the outstanding compound having anticancer activity. Quite a few other cancer treatments have natural origins. Even this year a new cancer fighting drug was introduced that has its origin from soil bacteria found only in the mud of the Zambezi River. However, much of modern cancer research has moved away from natural products into technology. Research has focused on using technology to find new ways to target cancer cells specifically, while leaving healthy cells intact – a technique that promises to make cancer treatments more effective while reducing unpleasant side effects.


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