Thursday, July 25, 2013
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culture and mouse studies suggest inhibiting oxidative phosphorylation could
help treat drug-resistant melanoma. In cultured, drug-resistant melanoma
cells that highly expressed jumonji AT
rich interactive domain 1B (JARID1B;
multiple proteins involved in oxidative phosphorylation were overexpressed
compared with expression in control cells. A series of compounds that inhibit
mitochondrial ATP production increased cell death compared with vehicle. In
xenograft mouse models for melanoma, combining inhibitors of oxidative
phosphorylation with anticancer drugs decreased tumor growth compared with
either set of compounds alone. Next steps include understanding the basis for
mitochondria-mediated drug resistance in JARID1B-overexpressing cells and
could include a clinical trial of Zelboraf
Sankyo Co. Ltd. and Chugai
Pharmaceutical Co. Ltd. market Zelboraf vemurafenib, a
small molecule inhibitor of BRAF
V600E, for melanoma.
Phenformin, a biguanide that inhibits oxidative
phosphorylation, is a generic diabetes drug.
Published online July 25, 2013
Patent and licensing status
Roesch, A. et al. Cancer
published online June 10, 2013;
Contact: Meenhard Herlyn, The Wistar Institute,
Contact: Alexander Roesch, Saarland University Hospital,
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