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A Genome-Wide Association Study in Patients Experiencing Breast Events While Receiving Adjuvant Aromatase Inhibitors for Early Breast Cancer on NCIC CTG Trial MA.27.

ABSTRACT: A Genome-Wide Association Study in Patients Experiencing Breast Events While Receiving Adjuvant Aromatase Inhibitors for Early Breast Cancer on NCIC CTG Trial MA.27.

PROVIDER: PRJNA306194 | ENA |

REPOSITORIES: ENA

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Project description:A Genome-Wide Association Study in Patients Experiencing Breast Events While Receiving Adjuvant Aromatase Inhibitors for Early Breast Cancer on NCIC CTG Trial MA.27.

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GDNF-RET signaling as a target in aromatase inhibitor resistant breast cancers

Project description:Understanding the complex molecular mechanisms underlying resistance to endocrine therapy is a major challenge in the treatment of estrogen receptor-positive (ER+) breast cancers. We have previously demonstrated that glial cell line-derived neurotrophic factor (GDNF) signaling via the receptor tyrosine kinase RET promotes estrogen independent activation of ER. Here we have addressed the relevance of GDNF-RET signaling in response to aromatase inhibitor treatment and explored the efficacy of using RET inhibitors in breast cancer models of aromatase inhibitor response and resistance. A GDNF-response gene set, identified from gene expression profiling, was demonstrated to be an independent prognostic marker of poor patient outcome and, importantly, to be predictive of poor response to aromatase inhibitor treatment and development of resistance. The relevance of these findings was validated first by demonstrating an association of RET protein expression in an independent cohort of aromatase inhibitor resistant patient samples. Second, in in vitro models, GDNF-mediated RET signaling was demonstrated to enhance the survival of aromatase inhibitor resistant cells and to increase resistance in aromatase inhibitor sensitive cells. These effects could be reversed by targeting GDNF/RET signaling with the RET selective inhibitor NVP-BBT594 thus identifying GDNF-RET signaling as a potential therapeutic target, particularly in breast cancers resistant to aromatase inhibitors.<br>MCF7 cells were E2-deprived by culturing in phenol red-free RPMI 1640 supplemented with 10% DCC for 3 days and then serum-starved overnight in the presence or absence of fulvestrant (ICI182,780) (100 nM). The following day, cells were treated with GDNF (20 ng/ml) for 0, 4, 8, 24 and 48 hours in the presence or absence of fulvestrant (ICI182,780) (100 nM).

2013-01-17 | E-MEXP-3662 | biostudies-arrayexpress

NCTN: Letrozole in Breast Cancer Who Have Received 5 Years of Aromatase Inhibitor Therapy (NCIC-MA.17R)

Project description:NCTN: Letrozole in Breast Cancer Who Have Received 5 Years of Aromatase Inhibitor Therapy (NCIC-MA.17R)

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NCTN: Letrozole in Breast Cancer Who Have Received 5 Years of Aromatase Inhibitor Therapy (NCIC-MA.17R)

Project description:NCTN: Letrozole in Breast Cancer Who Have Received 5 Years of Aromatase Inhibitor Therapy (NCIC-MA.17R)

| PRJNA1307685 | ENA

Transcription profiling of human breast cancer biopsies taken before and after patients were treated with aromatase inhibitors

Project description:Molecular response to Aromatase Inhibitor Treatment in Primary Breast Cancer

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Molecular profiling of aromatase inhibitor-treated post-menopausal breast tumors identifies immunerelated correlates of resistance

Project description:To identify in clinical breast cancer those genes and pathways most associated with resistance to aromatase inhibitors by examining the global transcriptional effects of aromatase inhibitor (AI) treatment. Analysis of gene-expression measured in core-cut biopsies at baseline and surgery from patients received 2-week’s presurgical AI revealed: i) the molecular response to AI treatment varies greatly between patients, consistent with the variable clinical benefit from AI treatment; ii) higher baseline expression of an inflammatory signature is associated with poor antiproliferative response, and should be assessed further as a novel biomarker and potential target for AI-treated patients.

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Global mapping of estrogen receptor and histone modifications in breast tumor samples uncovers distinct patterns for aromatase inhibitor resistance

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Expression profiling of response to first-line aromatase inhibitor therapy

Project description:Fresh-frozen primary cancer specimens of 107 breast cancer patients whose metastases were treated with first-line aromatase inhibitors were evaluated for their whole genome mRNA expression profiles.

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Global mapping of estrogen receptor and histone modifications in breast tumor samples uncovers distinct patterns for aromatase inhibitor resistance

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