Reference Detail

Ref Type Journal Article
PMID (25667100)
Authors Hole S, Pedersen AM, Lykkesfeldt AE, Yde CW
Title Aurora kinase A and B as new treatment targets in aromatase inhibitor-resistant breast cancer cells.
Journal Breast cancer research and treatment
Vol 149
Issue 3
Date 2015 Feb
URL
Abstract Text Aromatase inhibitors (AIs) are used for treatment of estrogen receptor α (ER)-positive breast cancer; however, resistance is a major obstacle for optimal outcome. This preclinical study aimed at identifying potential new treatment targets in AI-resistant breast cancer cells. Parental MCF-7 breast cancer cells and four newly established cell lines, resistant to the AIs exemestane or letrozole, were used for a functional kinase inhibitor screen. A library comprising 195 different compounds was tested for preferential growth inhibition of AI-resistant cell lines. Selected targets were validated by analysis of cell growth, cell cycle phase distribution, protein expression, and subcellular localization. We identified 24 compounds, including several inhibitors of Aurora kinases e.g., JNJ-7706621 and barasertib. Protein expression of Aurora kinase A and B was found upregulated in AI-resistant cells compared with MCF-7, and knockdown studies showed that Aurora kinase A was essential for AI-resistant cell growth. In AI-resistant cell lines, the clinically relevant Aurora kinase inhibitors alisertib and danusertib blocked cell cycle progression at the G2/M phase, interfered with chromosome alignment and spindle pole formation, and resulted in preferential growth inhibition compared with parental MCF-7 cells. Even further growth inhibition was obtained when combining the Aurora kinase inhibitors with the antiestrogen fulvestrant. Our study is the first to demonstrate that Aurora kinase A and B may be treatment targets in AI-resistant cells, and our data suggest that therapy targeting both ER and Aurora kinases may be a potent treatment strategy for overcoming AI resistance in breast cancer.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

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 breast cancer not applicable Alisertib Preclinical - Cell culture Actionable In a preclinical study, Alisertib (MLN8237) disrupted cell cycle progression and inhibited growth of breast cancer cell lines, with preferential inhibition of aromatase inhibitor-resistant cell lines (PMID: 25667100). 25667100
Unknown unknown breast cancer not applicable Alisertib Preclinical - Pdx & cell culture Actionable In a preclinical study, treatment with Alisertib (MLN8237) resulted in reduced cell migration of breast cancer cells in cell motility assays and in patient derived xenograft (PDX) models of breast cancer, improved survival and reduced metastasis was observed (PMID: 27235164). 27235164
Unknown unknown breast cancer not applicable Danusertib + Fulvestrant Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Danusertib (PHA-739358) and Faslodex (fulvestrant) resulted in increased growth inhibition in aromatase inhibitor-resistant breast cancer cell lines compared to either agent alone (PMID: 25667100). 25667100
Unknown unknown breast cancer not applicable Fulvestrant + JNJ-7706621 Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of JNJ-7706621 and Faslodex (fulvestrant) resulted in increased growth inhibition in aromatase inhibitor-resistant breast cancer cell lines compared to either agent alone (PMID: 25667100). 25667100
Unknown unknown breast cancer not applicable Alisertib + Fulvestrant Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Alisertib (MLN8237) and Faslodex (fulvestrant) resulted in increased growth inhibition in aromatase inhibitor-resistant breast cancer cell lines compared to either agent alone (PMID: 25667100). 25667100
Unknown unknown breast cancer not applicable Barasertib Preclinical - Cell culture Actionable In a preclinical study, Barasertib (AZD1152) treatment disrupted cell cycle progression and inhibited growth of breast cancer cell lines in culture, with preferential inhibition of aromatase inhibitor-resistant cell lines (PMID: 25667100). 25667100
Unknown unknown breast cancer not applicable Danusertib Preclinical - Cell culture Actionable In a preclinical study, Danusertib (PHA-739358) disrupted cell cycle progression and inhibited growth of breast cancer cell lines, with preferential inhibition of aromatase inhibitor-resistant cell lines (PMID: 25667100). 25667100
Unknown unknown colorectal cancer not applicable Navitoclax + TAK-901 Preclinical - Cell culture Actionable In a preclinical study, the combination of TAK-901 and ABT-263 demonstrated synergy in inhibiting proliferation of colorectal cancer cell lines in culture (PMID: 25667100). 25667100
Unknown unknown breast cancer not applicable JNJ-7706621 Preclinical - Cell culture Actionable In a preclinical study, JNJ-7706621 disrupted cell cycle progression and inhibited growth of breast cancer cell lines in culture, with preferential inhibition of aromatase inhibitor-resistant cell lines (PMID: 25667100). 25667100