The bromodomain and extraterminal (BET) domain inhibitor class of drugs has shown that, in combination with cisplatin, it can suppress activity of the enzyme ALDH in epithelial ovarian cancer cells. ALDH activity increases as a result of higher levels of ALDH1A1 protein created by cancer stem-like cells, contributing to chemo resistance. By suppressing the enzyme, the effect can be reversed, the study, published in Cancer Research, shows.
Cisplatin is an effective platinum-based chemotherapy, but it does increase ALDH levels on its own, so over time the tumor builds a resistance. But in combination with BET, the effect was offset.
In mice with epithelial ovarian cancer cells, those receiving a combination of the drugs as opposed to cisplatin alone showed significantly extended survival and delayed tumor outgrowth.
“There is a tremendous need for novel therapeutic strategies for patients with chemotherapy resistant ovarian cancer, given the prevalence of the clinical challenge and the limited number of other options available,” lead author Rugang Zhang said. “This study demonstrates how an existing class of targeted therapies could be used to potentiate the tumor suppression induced by cisplatin.”
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