Modifying natural molecules to maximize their therapeutic potential and minimize their side effects is a major focus of Memorial Sloan-Kettering Cancer Center chemists. In a promising example of that approach, scientists at the Sloan-Kettering Institute have found that one synthetic substance, called Fludelone (Flu), eradicated human myelomas (bone marrow cancers) grafted into mice. Flu is particularly effective against tumor cells in animal models of aggressive disease. The findings appeared in the July 26 issue of the Proceedings of the National Academy of Sciences. [PubMed Abstract and Full Text]
Samuel J. Danishefsky, a co-author of the study, called the synthesis of Flu "the fruit of the Center's large investment in chemistry -- an investment that will yield major benefits to patients."
Flu is a synthetic epothilone developed in collaboration with Sloan-Kettering Institute pharmacologist Ting-Chao Chou. These chemicals, found in soil bacteria, prevent cells from dividing properly. Their effect is similar to that of paclitaxel (Taxol®), which is used in patients with advanced breast and ovarian cancer. However, epothilones are less toxic to normal cells than paclitaxel and kill tumors that resist it and other drugs. In laboratory work, Flu has been remarkably potent against many human cancers, including breast, ovarian, colon, and now multiple myeloma. "Fludelone is not ready to be tested in patients, but two similar Sloan-Kettering drugs are in early clinical trials," said study co-author Malcolm A.S. Moore.
