A joint Fermilab/SLAC publication

Particle accelerators help develop new cancer fighting drug

08/26/11

Light sources are the ultimate app for particle physics. Researchers around the world use the powerful X-ray beams that light sources create for materials science, protein structure analysis, historical research, pharmaceutical research and drug development and the list keeps going. Argonne National Laboratory published the following story on August 25, 2011 about contributions that the Advanced Photon Source made to developing a new drug to treat skin cancer. For more examples about the applications of particle physics, visit Accelerators for America's Future

Powerful x-ray technology developed at the U.S. Department of Energy Office of Science’s (DOE-SC's) national laboratories, including the Advanced Photon Source at Argonne National Laboratory, has enabled the discovery of a groundbreaking new drug treatment for malignant melanoma, the deadliest form of skin cancer. The drug, Zelboraf (vemurafenib), received Food and Drug Administration (FDA) approval on Wednesday, August 17, 2011. In revealing the structures of diseased and disease-causing molecules at their basic level, the DOE-SC’s extremely bright x-ray light sources enable scientists to develop potential new treatments.

The protein crystallographic structure of the new anti-cancer drug, vemurafenib, is the green honeycomb structure at middle left. Four dotted red lines show where it attaches to a target area in the mutated enzyme, disabling it from promoting the growth of tumors. Image courtesy of Plexxikon Inc.

“This technology is a wonderful example of how innovations at our national laboratories lead to discoveries in a wide variety of fields,” said Energy Secretary Steven Chu. “In this case, we are pleased to have been involved in research that has shown great promise in the battle against life-threatening melanoma.”

An increasing number of drug discovery companies and medical researchers are turning to the powerful x-ray facilities at the DOE national laboratories to probe the causes of disease and develop new treatments by revealing new insights into a wide range of diseases. Researchers from Plexxikon Inc., the drug discovery company that developed the melanoma treatment, used x-ray light sources at Argonne and two other DOE national laboratories—SLAC National Accelerator Laboratory and Lawrence Berkeley National Laboratory—to determine the specific, three-dimensional protein structure of a mutated enzyme that tells melanoma cancer cells to multiply uncontrollably. The research at the APS was carried out at the Structural Biology Center Collaborative Access Team x-ray beamline 19-BM.

The researchers used the technique called macromolecular x-ray crystallography to determine the protein structure in order to develop a drug that would prevent the enzyme from multiplying. The newly FDA-approved drug, Zelboraf (vemurafenib), was extremely successful during clinical trials in disrupting the disease and extending the lives of those diagnosed with it.

“Plexxikon’s drug discovery approach is critically dependent on harnessing the power of x-ray crystallography, and the role of DOE facilities in enabling the development of compounds like vemurafenib has been fundamental,” said Gideon Bollag, Senior Vice President for Research at Plexxikon. “With the insight we gain from the three-dimensional structures, we have an atomic road map to rationally optimize our drug candidates.”

In addition to this treatment for melanoma, the x-ray light sources at the DOE-SC labs have revealed new insights into diseases such as Alzheimer's disease, swine flu, autoimmune disorders, bird flu, hepatitis, and the common cold.

The original DOE press release can be read here.

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