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Cancer signaling pathway blocker

April 10, 2015 | Yan Su

Researchers at Vanderbilt University have discovered a new way to inhibit Hedgehog (Hh) signaling, an important regulatory pathway for vertebrate development – and cancer. Abnormal regulation of this pathway leads to several human malignancies, including small cell lung cancer and pancreatic cancer, and therefore it is a potential drug target for cancer.

Small molecules have been developed that target the G protein-coupled receptor Smoothened (Smo), one of the components in the Hh pathway, but their clinical efficacy is limited.

Using a chemical genetic zebrafish screen, Charles Hong, M.D., Ph.D., and colleagues identified a small molecule drug, eggmanone, which targets phosphodiesterase (PDE) 4, a protein downstream of Smo. PDE4 previously has been implicated as a driver of central nervous system tumors such as glioblastoma as well as lung and breast tumors, but this is the first time it has been identified as a potential drug target to block the Hh pathway.

Their report was published online March 26 in the journal Cell Reports.

The research was supported in part by National Institutes of Health grant R01HL104040.