MAPK pathway activation leads to Bim loss and histone deacetylase inhibitor resistance: rationale to combine romidepsin with an MEK inhibitor
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چکیده
منابع مشابه
Electrocardiographic effects of class 1 selective histone deacetylase inhibitor romidepsin
Romidepsin is a histone deacetylase inhibitor approved by the FDA for the treatment of patients with cutaneous or peripheral T-cell lymphoma who have received prior systemic therapy. The objective of this analysis was to evaluate the potential QTc effects of romidepsin. Patients with advanced malignancy received 4-h infusions of 14 mg/m(2) romidepsin on days 1, 8, and 15 of a 28-day cycle. In c...
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We previously demonstrated activation of the mitogen-activated protein kinase (MAPK) pathway in a series of romidepsin-selected T-cell lymphoma cell lines as a mechanism of resistance to the histone deacetylase inhibitor (HDI), romidepsin. As Ras mutation leads to activation of both the MAPK and the phosphoinositide 3-kinase (PI3K) pathway, we examined whether combining romidepsin with small mo...
متن کاملCharacterisation of the novel apoptotic and therapeutic activities of the histone deacetylase inhibitor romidepsin.
Histone deacetylase inhibitors (HDACi) are compounds that target the epigenome and cause tumor cell-selective apoptosis. A large number of these agents that have different chemical structures and can target multiple HDACs are being testing in clinical trials and vorinostat is now an approved drug for the treatment of cutaneous T-cell lymphoma. Although these agents are showing promise for the t...
متن کاملUse of class I histone deacetylase inhibitor romidepsin in combination regimens
Histone deacetylase (HDAC) inhibitors are epigenetic-modifying agents that have shown promise as anticancer therapies. Several HDAC inhibitors have been approved by the US Food and Drug Administration (FDA) as single-agent therapies to treat T-cell lymphoma. The synergistic combination of HDAC inhibitors with other anticancer agents has the potential to constitute treatment regimens with enhanc...
متن کاملTranscriptional induction of GRP78/BiP by histone deacetylase inhibitors and resistance to histone deacetylase inhibitor-induced apoptosis.
Histone deacetylase (HDAC) inhibitors are emerging as effective therapies in the treatment of cancer, and the role of HDACs in the regulation of promoters is rapidly expanding. GRP78/BiP is a stress inducible endoplasmic reticulum (ER) chaperone with antiapoptotic properties. We present here the mechanism for repression of the Grp78 promoter by HDAC1. Our studies reveal that HDAC inhibitors spe...
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ژورنال
عنوان ژورنال: Blood
سال: 2013
ISSN: 0006-4971,1528-0020
DOI: 10.1182/blood-2012-08-449140