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|Ref Type||Journal Article|
|Authors||Arora N, Alsaied O, Dauer P, Majumder K, Modi S, Giri B, Dudeja V, Banerjee S, Von Hoff D, Saluja A|
|Title||Downregulation of Sp1 by Minnelide leads to decrease in HSP70 and decrease in tumor burden of gastric cancer.|
|Abstract Text||Gastric cancer is the third leading cause of cancer related mortality worldwide with poor survival rates. Even though a number of chemotherapeutic compounds have been used against this disease, stomach cancer has not been particularly sensitive to these drugs. In this study we have evaluated the effect of triptolide, a naturally derived diterpene triepoxide and its water soluble pro-drug Minnelide on several gastric adenocarcinoma cell lines both as monotherapy and in combination with CPT-11.Gastric cancer cell lines MKN28 and MKN45 were treated with varying doses of triptolide in vitro. Cell viability was measured using MTT based assay kit. Apoptotic cell death was assayed by measuring caspase activity. Effect of the triptolide pro-drug, Minnelide, was evaluated by implanting the gastric cancer cells subcutaneously in athymic nude mice.Gastric cancer cell lines MKN28 and MKN45 cells exhibited decreased cell viability and increased apoptosis when treated with varying doses of triptolide in vitro. When implanted in athymic nude mice, treatment with Minnelide reduced tumor burden in both MKN28 derived tumors as well as MKN45 derived tumors. Additionally, we also evaluated Minnelide as a single agent and in combination with CPT-11 in the NCI-N87 human gastric tumor xenograft model.Our results indicated that the combination of Minnelide with CPT-11 resulted in significantly smaller tumors compared to control. These studies are extremely encouraging as Minnelide is currently undergoing phase 1 clinical trials for gastrointestinal cancers.|
|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|
|Minnelide||Minnelide is a water-soluble prodrug of the naturally derived diterpene triepoxide, triptolide, which induces apoptosis and inhibits cell proliferation, leading to reduced tumor growth (PMID: 28192510, PMID: 32733649).|
|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||gastric adenocarcinoma||not applicable||Minnelide||Preclinical - Cell line xenograft||Actionable||In a preclinical study, Minnelide treatment inhibited tumor growth and induced regression in gastric adenocarcinoma cell line xenograft models (PMID: 28192510).||28192510|
|Unknown unknown||gastric adenocarcinoma||not applicable||Irinotecan + Minnelide||Preclinical - Cell line xenograft||Actionable||In a preclinical study, Minnelide and Camptosar (irinotecan) combination treatment resulted in increased inhibition of tumor growth in a cell line xenograft model of gastric adenocarcinoma compared to either Minnelide or Camptosar (irinotecan) treatment alone (PMID: 28192510).||28192510|
|Unknown unknown||gastric adenocarcinoma||not applicable||Triptolide||Preclinical - Cell culture||Actionable||In a preclinical study, treatment with Triptolide (C1572) induced apoptotic cell death and resulted in decreased cell viability in gastric adenocarcinoma cell lines in culture (PMID: 28192510).||28192510|