Abstract
Repurposing Tecfidera for cancer.
Highlights
The compound dimethyl fumarate (DMF) has been an approved drug in Europe for several decades as a therapeutic for psoriasis and relapsing-remitting multiple sclerosis (MS)
In our earliest work with mono methyl fumarate (MMF) we found the drug could synergistically kill tumor cells by interacting with proteasome inhibitors, the NSAID celecoxib (Celebrex®) as well as with the standard of care brain tumor therapeutics temozolomide (Temodar®) and ionizing radiation
Unlike its combination with ruxolitinib, MMF combined with proteasome inhibitors caused activation of the death receptor CD95 which signaled through the mitochondria to cause AIF-dependent, but caspase 3-independent, tumor cell execution
Summary
The compound dimethyl fumarate (DMF) has been an approved drug in Europe for several decades as a therapeutic for psoriasis and relapsing-remitting multiple sclerosis (MS). In our earliest work with MMF we found the drug could synergistically kill tumor cells by interacting with proteasome inhibitors, the NSAID celecoxib (Celebrex®) as well as with the standard of care brain tumor therapeutics temozolomide (Temodar®) and ionizing radiation. When combined with proteasome inhibitors, MMF again was shown to inactivate ERK1/2, AKT, STAT3 as well as mTOR, which resulted in increased levels of toxic autophagosome production.
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