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|Ref Type||Journal Article|
|Authors||Zakharia K, Miyabe K, Wang Y, Wu D, Moser CD, Borad MJ, Roberts LR|
|Title||Preclinical In Vitro and In Vivo Evidence of an Antitumor Effect of CX-4945, a Casein Kinase II Inhibitor, in Cholangiocarcinoma.|
|Date||2018 Oct 10|
|Abstract Text||We investigated the antitumor effect of the casein kinase II (CK2) inhibitor CX-4945 on cholangiocarcinoma (CCA).We assessed the effect of CX-4945 alone and/or in combination with gemcitabine and cisplatin on cell viability, colony formation, and apoptosis of CCA cell lines and on in vivo growth of HuCCT1 xenografts.CX-4945 dose-dependently decreased viability of HuCCT1, EGI-1, and Liv27 and decreased phospho-AKT/total AKT and phospho-PTEN/total PTEN ratios. CX-4945 significantly increased caspase 3/7 activity in a dose- and time-dependent manner. CX-4945 significantly enhanced the effect of gemcitabine or cisplatin on HuCCT1, EGI-1, and Liv27 cells and inhibited the phosphorylation of DNA repairing enzymes XRCC1 and MDC1. Further, CX-4945 alone significantly inhibited growth of HuCCT1 mouse xenograft tumors. Combining CX-4945 with gemcitabine and cisplatin was more potent than CX-4945 alone or gemcitabine/cisplatin. The effect of CX-4945 on cell proliferation, apoptosis, the PI3K/AKT pathway, and DNA repair was confirmed in the mouse xenografts.CX-4945 has an antiproliferative effect on CCA and enhances the effect of gemcitabine and cisplatin through its inhibitory effect on the PI3K/AKT pathway and DNA repair.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||cholangiocarcinoma||not applicable||Silmitasertib||Preclinical - Cell line xenograft||Actionable||In a preclinical study, the protein kinase CK2 inhibitor, Silmitasertib (CX-4945), inhibited tumor growth and increased survival of cholangiocarcinoma cell line xenograft models (PMID: 30316146).||30316146|
|Unknown unknown||cholangiocarcinoma||not applicable||Cisplatin + Gemcitabine + Silmitasertib||Preclinical - Cell line xenograft||Actionable||In a preclinical study, the protein kinase CK2 inhibitor, Silmitasertib (CX-4945), in combination with Platinol (cisplatin) and Gemzar (gemcitabine), inhibited tumor growth and increased survival of cholangiocarcinoma cell line xenograft models, to a greater extent than either compound alone (PMID: 30316146).||30316146|