Romidepsin, Decitabine Combo Effective in Drug Resistant Solid Tumors

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(ChemotherapyAdvisor) – Combating metastatic solid tumors, such as clear cell renal cell carcinoma (ccRCC) and triple negative breast cancer (TNBC), might be more effective with combinatorial regimens that include romidepsin and decitabine, according to researchers of the Mayo Clinic, Rochester, MN. This conclusion is based on a study entitled “Re-expression of tumor suppressor, sFRP1, leads to antitumor synergy of combined HDAC and methyltransferase inhibitors in chemoresistant cancers,” which was published in Molecular Cancer Therapeutics on July 23.

In this study, the investigators aimed to identify new therapeutic regimens for the treatment of metastatic solid tumors, which are aggressive and mostly drug resistant; examples include ccRCC and TNBC. To meet this aim, the investigators treated 2 cancer cell lines—ccRCC and TNBC—with the HDAC inhibitor romidepsin and the methyltransferase inhibitor decitabine, both of which are FDA-approved for the treatment of various hematologic malignancies.

After treatment with these 2 inhibitors, growth of metastatic TNBC and stage 4 ccRCC cell lines was inhibited and cell death (apoptosis) was induced. More importantly, the investigators observed the synergistic re-expression of the tumor suppressor gene secreted frizzled-related protein one (sFRP1). Turning off expression of sFRP1 prior to treatment enabled the investigators to show that this tumor suppressor gene mediates the growth inhibitory and apoptotic activity of combined romidepsin/decitabine. “Furthermore, addition of recombinant sFRP1 to ccRCC or TNBC cells inhibits cell growth in a dose-dependent manner through the induction of apoptosis, thus identifying that epigenetic silencing of sFRP1 contributes to renal and breast cancer cell survival,” the investigators wrote.

The investigators concluded that “combinatorial treatment with romidepsin and decitabine in drug resistant tumors is a promising treatment strategy.”

Abstract

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