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Ref Type Journal Article
PMID (27196760)
Authors Alvero AB, Heaton A, Lima E, Pitruzzello M, Sumi N, Yang-Hartwich Y, Cardenas C, Steinmacher S, Silasi DA, Brown D, Mor G
Title TRX-E-002-1 Induces c-Jun-Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo.
Journal Molecular cancer therapeutics
Vol 15
Issue 6
Date 2016 Jun
Abstract Text Chemoresistance is a major hurdle in the management of patients with epithelial ovarian cancer and is responsible for its high mortality. Studies have shown that chemoresistance is due to the presence of a subgroup of cancer cells with stemness properties and a high capacity for tumor repair. We have developed a library of super-benzopyran analogues to generate potent compounds that can induce cell death in chemoresistant cancer stem cells. TRX-E-002-1 is identified as the most potent analogue and can induce cell death in all chemoresistant CD44(+)/MyD88(+) ovarian cancer stem cells tested (IC50 = 50 nmol/L). TRX-E-002-1 is also potent against spheroid cultures formed from cancer stem cells, chemosensitive CD44(-)/MyD88(-) ovarian cancer cells, and heterogeneous cultures of ovarian cancer cells. Cell death was associated with the phosphorylation and increased levels of c-Jun and induction of caspases. In vivo, TRX-E-002-1 given as daily intraperitoneal monotherapy at 100 mg/kg significantly decreased intraperitoneal tumor burden compared with vehicle control. When given in combination with cisplatin, animals receiving the combination of cisplatin and TRX-E-002-1 showed decreased tumor burden compared with each monotherapy. Finally, TRX-E-002-1 given as maintenance treatment after paclitaxel significantly delayed disease recurrence. Our results suggest that TRX-E-002-1 may fill the current need for better therapeutic options in the control and management of recurrent ovarian cancer and may help improve patient survival. Mol Cancer Ther; 15(6); 1279-90. ©2016 AACR.


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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
TRX-E-002-1 TRX-E-002-1 1 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
TRX-E-002-1 Cantrixil Cantrixil (TRX-E-002-1) is a super-benzopyran analogue that demonstrates potent anti-proliferation activity through regulation of c-Jun and Mek signaling (PMID: 27196760, PMID: 28013349).
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 ovarian cancer not applicable Paclitaxel + TRX-E-002-1 Preclinical - Cell line xenograft Actionable In a preclinical study, TRX-E-002-1 given as a maintenance treatment after Taxol (paclitaxel) treatment resulted in less tumor recurrence compared to placebo in cell line xenograft models of ovarian cancer (PMID: 27196760). 27196760
Unknown unknown ovarian cancer not applicable TRX-E-002-1 Preclinical - Cell line xenograft Actionable In a preclinical study, TRX-E-002-1 inhibited proliferation and induced apoptosis in chemoresistant human ovarian cancer cell lines in culture, and reduced tumor size in ovarian cancer cell line xenograft models (PMID: 27196760). 27196760
Unknown unknown ovarian cancer not applicable Cisplatin + TRX-E-002-1 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of TRX-E-002-1 and Platinol (cisplatin) synergized to induce cell death in human chemoresistant ovarian cancer cell lines in culture and decreased tumor burden in xenograft models (PMID: 27196760). 27196760