Reference Detail

Ref Type Journal Article
PMID (28179288)
Authors Murai S, Matuszkiewicz J, Okuzono Y, Miya H, DE Jong R
Title Aurora B Inhibitor TAK-901 Synergizes with BCL-xL Inhibition by Inducing Active BAX in Cancer Cells.
Journal Anticancer research
Vol 37
Issue 2
Date 2017 02
URL
Abstract Text Aurora B kinase plays an essential role in chromosome segregation and cytokinesis, and is dysregulated in many cancer types, making it an attractive therapeutic target. TAK-901 is a potent aurora B inhibitor that showed efficacy in both in vitro and in vivo oncology models.We conducted a synthetic lethal siRNA screening to identify the genes that, when silenced, can potentiate the cell growth-inhibitory effect of TAK-901.B-cell lymphoma-extra large (BCL-xL) depletion by siRNA or chemical inhibition synergized with TAK-901 in cancer cell lines. As a mechanism of synthetic lethality, active BCL2 associated X, apoptosis regulator (BAX) was induced by TAK-901. BCL-xL protected cells from BAX-dependent apoptosis induction. Therefore, TAK-901 sensitizes cancer cells to BCL-xL inhibition.Polyploid cells induced by TAK-901 are vulnerable to BCL-xL inhibition. Our findings may have an impact on combination strategies with aurora B inhibitors in clinical studies.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Therapy Description
Drug Name Trade Name Synonyms Drug Classes Drug Description
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 prostate cancer not applicable Navitoclax + TAK-901 Preclinical - Cell culture Actionable In a preclinical study, the combination of TAK-901 and Navitoclax (ABT-263) resulted in a synergistic effect, demonstrating reduced cell viability of prostate cancer cells in culture (PMID: 28179288). 28179288
Unknown unknown non-small cell lung carcinoma not applicable Navitoclax + TAK-901 Preclinical - Cell culture Actionable In a preclinical study, the combination of TAK-901 and Navitoclax (ABT-263) resulted in a synergistic effect, demonstrating reduced cell viability of non-small cell lung cancer cells in culture (PMID: 28179288). 28179288
Unknown unknown colorectal cancer not applicable Barasertib + Navitoclax Preclinical - Cell culture Actionable In a preclinical study, the combination of Barasertib (AZD1152) and Navitoclax (ABT-263) resulted in synergy, demonstrating inhibition of cell proliferation and increased apoptotic activity in colorectal cancer cells in culture (PMID: 28179288). 28179288
Unknown unknown non-small cell lung carcinoma not applicable Barasertib + Navitoclax Preclinical - Cell culture Actionable In a preclinical study, the combination of Barasertib (AZD1152) and Navitoclax (ABT-263) resulted in synergy, inhibiting proliferation of non-small cell lung carcinoma cells in culture (PMID: 28179288). 28179288
Unknown unknown prostate cancer not applicable Barasertib + Navitoclax Preclinical - Cell culture Actionable In a preclinical study, the combination of Barasertib (AZD1152) and Navitoclax (ABT-263) resulted in synergy, inhibiting proliferation of prostate cancer cells in culture (PMID: 28179288). 28179288