A5017933040- Estrogen and related hormone effects
- Advanced Breast Cancer Therapies
- HER2/EGFR in Cancer Research
- Brain Metastases and Treatment
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Mechanisms of cancer metastasis
- RNA modifications and cancer
- Histone Deacetylase Inhibitors Research
- Cell Adhesion Molecules Research
- Genomics and Chromatin Dynamics
- Cytokine Signaling Pathways and Interactions
- Breast Cancer Treatment Studies
- Cancer-related Molecular Pathways
- Click Chemistry and Applications
- Peptidase Inhibition and Analysis
- Cancer therapeutics and mechanisms
- Lung Cancer Treatments and Mutations
- Inflammatory mediators and NSAID effects
- S100 Proteins and Annexins
- Cancer survivorship and care
- Cancer Treatment and Pharmacology
- Lung Cancer Research Studies
Royal College of Surgeons in Ireland
2016-2025
Beaumont Hospital
2008-2025
Wesley Hospital
2017-2025
University of Medicine and Health Sciences
2024-2025
University College Dublin
2005-2024
St. Vincent's University Hospital
2002-2024
Royal Liverpool University Hospital
2019
University of Liverpool
2019
Walton Centre
2019
Clatterbridge Cancer Centre NHS Foundation Trust
2019
Amplified-in-breast cancer 1 (AIB1) is an overexpressed transcriptional coactivator in breast cancer. Although overproduced AIB1 oncogenic, its role and underlying mechanisms metastasis remain unclear. Here, mammary tumorigenesis lung were investigated wild-type (WT) AIB1(-/-) mice harboring the mouse tumor virus-polyomavirus middle T (PyMT) transgene. All WT/PyMT developed massive metastasis, but AIB1(-/-)/PyMT with comparable tumors had significantly less metastasis. The recipient...
Patients with breast cancer (BrCa) brain metastases (BrM) have limited therapeutic options. A better understanding of molecular alterations acquired in BrM could identify clinically actionable metastatic dependencies.
Breast cancer brain metastases (BrMs) are defined by complex adaptations to both adjuvant treatment regimens and the microenvironment. Consequences of these alterations remain poorly understood, as does their potential for clinical targeting. We utilized genome-wide molecular profiling identify therapeutic targets acquired in metastatic disease.Gene expression 21 patient-matched primary breast tumors associated was performed TrueSeq RNA-sequencing determine clinically actionable BrM target...
// Suzanne McFarlane 1 , Jonathan A. Coulter Paul Tibbits 2 Anthony O'Grady Cheryl Nicola Montgomery Ashleigh Hill Helen O. McCarthy 4 Leonie S. Young Elaine W. Kay Clare M. Isacke 3 David J.J. Waugh Centre for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Breakthrough Breast Centre, The Institute Research, London, UK School Pharmacy, Correspondence to: Waugh, e-mail: d.waugh@qub.ac.uk Keywords:...
Abstract The molecular events and transcriptional plasticity driving brain metastasis in clinically relevant breast tumor subtypes has not been determined. Here we comprehensively dissect genomic, transcriptomic clinical data patient-matched longitudinal samples, unravel distinct programs enriched metastasis. We report on subtype specific hub genes functional processes, central to disease-affected networks Importantly, luminal metastases identify homologous recombination deficiency operative...
Abstract Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and associated toxicity have questioned clinical impact of this approach emphasized need alternative treatments. Given limited therapeutic options available these poor understanding molecular mechanisms underlying resistance metastatic lesions to WBRT, we sought uncover actionable targets biomarkers that could help refine patient...
In the last decade, poly (ADP-ribose) polymerase (PARP) inhibitors have been approved in treatment of several cancers, such as breast and ovarian cancer. This article aims to discuss current uses, limitations, future directions for PARP (PARPis) Following results OlympiAD EMBRACA trials, PARPis were HER2-negative cancer with a germline BRCA mutation. We reviewed this class drugs' mechanism action, efficacy, well further studies that discussed resistance, impaired homologous recombination...
In human breast cancer, the growth factor receptor HER2 is associated with disease progression and resistance to endocrine treatment. Growth induced mitogen activated protein kinase activity can phosphorylate not only oestrogen receptor, but also its coactivator proteins AIB1 SRC-1.To determine whether insensitivity treatment in positive patients enhanced expression of proteins, transcriptional regulator, PEA3, coregulatory SRC-1, was assessed a cohort cancer known status.PEA3, AIB1, SRC-1...
Associations between p160 coactivator proteins and the development of resistance to endocrine treatment have been described. We hypothesized that nuclear receptor coregulatory may interact with nonsteroid receptors. investigated mitogen-activated protein kinase-activated transcription factors, Ets, as possible interaction for coactivators SRC-1 AIB1 corepressor NCoR in human breast cancer.Expression coexpression Ets was using immunohistochemistry immunofluorescence a cohort tumor patients (N...
Despite advances in cancer diagnosis and treatment have significantly improved survival rates, patients post-treatment-related health needs are often not adequately addressed by current services. The aim of the Women's Wellness after Cancer Program (WWACP), which is a digitised multimodal lifestyle intervention, to enhance health-related quality life women previously treated for blood, breast gynaecological cancers.A single-blinded, multi-centre randomized controlled trial recruited total...
Genome-wide screen identifies methylation of the estrogen-repressed HOXC10 gene as a determinant resistance to aromatase inhibitors in breast cancer.
These neuroendocrine studies were part of a series testing the hypotheses that 1) there may be reduced activity hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome and 2) low-dose augmentation with hydrocortisone therapy would improve core symptoms. We measured ACTH cortisol responses to human CRH, insulin stress test, d-fenfluramine 37 medication-free patients CDC-defined but no comorbid psychiatric disorders 28 healthy controls. also 24-h urinary free both groups. All (n = 37)...
The oestrogen receptor (ER) interacts with coactivator proteins to modulate genes central breast tumour progression. Oestrogen is encoded for by two genes, ER-α and ER-β. Although has been well characterized, the role of ER-β as a prognostic indicator remains unresolved. To determine isoform-specific expression ER coexpression activator proteins, we examined localisation ER-α, protein steroid 1 (SRC-1) immunohistochemistry immunofluorescence in cohort human cancer patients (n=150). Relative...
Estrogen receptor (ER)-α and ER-β function as transcription factors, both interact with nuclear regulatory proteins to enhance or inhibit transcription. We hypothesized that coregulators are expressed in breast cancer may be differentially recruited by ERs the presence of estrogen tamoxifen. was found more frequently node-negative patients (P < 0.05). Expression steroid coactivator-1 (SRC-1) associated nodal positivity 0.05) resistance endocrine treatment 0.001). The spatial coexpression...
This study investigates the role of p160 coactivators AIB1 and SRC-1 independently, their interactions with estrogen receptor, in development resistance to endocrine treatments.The expression p160s interactions, was analyzed by immunohistochemistry quantitative coassociation immunofluorescent microscopy, using cell lines, primary breast tumor cultures, a tissue microarray cancer samples from 560 patients.Coassociation receptor alpha increased LY2 endocrine-resistant line following treatment...
Abstract Mechanisms of acquired resistance to endocrine therapy in breast cancer, a major clinical challenge, are poorly understood. We have used mass spectrometry–based screen identify proteins that associated with the endocrine-resistant phenotype. In this study, we report identification novel pathway involving interactions developmental transcription HOXC11 steroid receptor coactivator protein SRC-1, which is strong predictor reduced disease-free survival cancer patients. and SRC-1...
Aromatase inhibitors (AI) are a standard-of-care treatment for postmenopausal, estrogen receptor-positive breast cancers. Although tumor recurrence on AI therapy occurs, the mechanisms underlying acquired resistance to AIs remain unknown. In this study, we examined cohort of endocrine-treated cancer patients and used cell line model letrozole. treated with first-line AI, hormone receptor switching between primary resistant tumors was common feature disease recurrence. Resistant cells...
Abstract In breast cancer, overexpression of the nuclear coactivator NCOA1 (SRC-1) is associated with disease recurrence and resistance to endocrine therapy. To examine impact on morphogenesis carcinogenesis in mammary gland (MG), we generated MMTV-hNCOA1 transgenic [Tg(NCOA1)] mice. context two distinct models did not affect morphology or tumor-forming capability MG epithelial cells. However, increased number circulating cancer cells efficiency lung metastasis. Mechanistic investigations...
Survivin has emerged as a unique regulator of cell death through its response to growth factors, such basic fibroblast factor (bFGF), which we have previously shown be mitogen-activated protein kinase (MAPK) dependent. The transcriptional complex myc/max is an oncogene that lies downstream the MAPK pathway, suggesting possible role in survivin’s regulation. In this study, investigated ability bFGF induce signalling effector transcription c-myc human breast cancer. Treatment SK-BR-3 cancer...