BioCentury
ARTICLE | Distillery Therapeutics

Cancer

September 27, 2018 3:43 PM UTC

Patient sample, cell culture and mouse studies suggest antagonizing AHR could help treat MM. In patients, high tumor levels of AHR correlated with poor survival. In multiple Velcade bortezomib-resistant and -sensitive human MM cell lines, clofazimine, which antagonizes AHR, increased cell death compared with vehicle, and in the Velcade-sensitive cell lines, an shRNA targeting AHR increased cell death compared with a scrambled control shRNA. In a xenograft mouse model of MM and a mouse model of spontaneous MM, clofazimine decreased disease burden compared with vehicle, with potency comparable to Velcade. Next steps include testing clofazimine in Velcade-resistant MM cell lines and in combination with other approved MM therapies.

The generic DNA-binding agent clofazimine is marketed outside the U.S. for leprosy and was withdrawn from the U.S. market in 2016. The compound is available in the U.S. under HHS’s National Hansen’s Disease Program (NHDP)...

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