UC Riverside researchers find potent chemical agents that can thwart cancer metastasis
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IMAGE: This is Maurizio Pellecchia of UC Riverside in the lab. view more 

Credit: Carrie Rosema

Recently, a research team led by Maurizio Pellecchia at the University of California, Riverside, discovered a way for chemotherapy drug paclitaxel to target migrating, or circulating, cancer cells, which are responsible for the development of tumor metastases.

The team was successful in getting the drug to piggyback on 123B9, an agent they devised to target an oncogene called EphA2 (ephrin type-A receptor 2). EphA2 spreads cancer by allowing malignant cells to migrate from the primary tumor into circulation and eventually to adhere to other tissues.

“But the exact mechanism by which 123B9 binds to its target remained elusive, which hampered the design of even more potent and effective agents,” Pellecchia said.

To meet this challenge, the team first derived a new and more effective EphA2 targeting agent, and subsequently, in collaboration with Jikui Song, an associate professor of biochemistry at UCR, determined the three-dimensional structure of this agent in complex with the ligand-binding domain of the receptor, hence allowing the team to see exactly how their agent interacts with EphA2. This allowed the team to further derive novel agents far more potent than 123B9.

“The

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