Scientists at Emory University, in collaboration with researchers at three national laboratories, have solved the structural puzzle of how an emerging class of promising cancer drugs works to halt cell division. The discovery potentially opens the door to the creation of more effective cancer treatments.
"Uncovering and mapping the structure of this model system will assist scientists around the world in creating new compounds that hopefully will lead to new cancer drugs," says researcher Jim Snyder, an Emory chemist and director of biostructural research at the university.
The results, reported in the Aug. 6 issue of the journal Science, include the first three-dimensional, atomic-scale images of the binding site where one of the drugs, epothilone A, interacts with a key protein controlling cell division.
The researchers have now examined two drug families – the epothilones and taxanes, which include the anti-cancer drug Taxol already in use. Both drugs work to halt the division of cancer cells by binding to the same site on a protein called tubulin that is involved in cell division. Tubulin is the major component of microtubules, the hollow cylinders that serve as a skeletal system for cells and a scaffold for chromosomes in the dividing cell. When epothilones or taxanes bind to tubulin, the protein loses its flexibility and the microtubules can no longer disassemble, halting cell division.