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Total synthesis of the clinical anticancer drug etoposide

Institution: California Institute of Technology
Investigator(s): Daniel Caspi, B.S. Chemistry
Award Cycle: 2004 (Cycle 13) Grant #: 13DT-0012 Award: $59,900
Subject Area: General Biomedical Science
Award Type: Dissertation Awards
Abstracts

Initial Award Abstract
Despite all the triumphs of modern medicine, lung cancer remains a terminal illness. The statistics are staggering: 85% of the people with lung cancer will die within 5 years of being diagnosed. With the highest fatality rate among the various cancer subtypes, accounting for nearly one-third of all cancer-related deaths, this disease claimed more than 150,000 lives over the past year in the United States alone. Not surprisingly, the great majority of lung cancer cases are attributed to smoking cigarettes. In the search for an ultimate cure, the development of new treatment options to prolong human life are of far-reaching consequence.

In the 1970’s, scientists at Sandoz Ltd. discovered the drug Etoposide, which today provides the first line of defense for people who suffer from lung cancer. Unfortunately, previous attempts at making Etoposide have generally proceeded through long, inefficient processes, so lung cancer patients must currently rely upon plant extracts to provide them with this important remedy. These restrictions have also prevented scientists from making many compounds related to Etoposide, which could have promising anticancer properties.

Therefore, this project proposes a new, highly efficient way to make Etoposide. The knowledge gained by this research has the potential to provide a cost-effective, and rapid way to obtain this valuable clinical therapeutic. Perhaps even more importantly, this approach allows for a great deal of flexibility so that compounds that are related to Etoposide that have never been previously made can be developed. These compounds could lead to the discovery of new, more effective, lung cancer treatments and would represent contributions to both organic chemistry as well as the treatment of tobacco-related diseases.