A5060253626- Advanced Breast Cancer Therapies
- Estrogen and related hormone effects
- Cancer-related Molecular Pathways
- Hippo pathway signaling and YAP/TAZ
- Cancer-related gene regulation
- HER2/EGFR in Cancer Research
- Cancer and Skin Lesions
- Nonmelanoma Skin Cancer Studies
- Gene expression and cancer classification
- Breast Cancer Treatment Studies
- Epigenetics and DNA Methylation
- Wnt/β-catenin signaling in development and cancer
- Prostate Cancer Treatment and Research
- Cancer Genomics and Diagnostics
- AI in cancer detection
- Cancer, Stress, Anesthesia, and Immune Response
- Tryptophan and brain disorders
- Vitamin D Research Studies
- Bioinformatics and Genomic Networks
- Metabolomics and Mass Spectrometry Studies
- Mass Spectrometry Techniques and Applications
- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Cancer Cells and Metastasis
- Ubiquitin and proteasome pathways
Garvan Institute of Medical Research
2018-2025
St Vincent's Clinic
2018-2025
UNSW Sydney
2018-2025
The Kinghorn Cancer Centre
2022-2023
University of Newcastle Australia
2015-2020
The University of Adelaide
2019
Hunter Medical Research Institute
2015-2017
Universidade Federal do Paraná
2015-2016
Universidade Federal de Santa Catarina
2016
Basal-like constitutes an important molecular subtype of breast cancer characterised by aggressive behaviour and a limited therapy response. The outcome patients within this is, however, divergent. Some individuals show increased risk dying in the first five years, others long-term survival over ten years after diagnosis. In study, we aim at identifying markers associated with basal-like patients' characterising subgroups distinct disease outcome.
Abstract Three-dimensional (3D) epigenome remodeling is an important mechanism of gene deregulation in cancer. However, its potential as a target to counteract therapy resistance remains largely unaddressed. Here, we show that epigenetic with decitabine (5-Aza-mC) suppresses tumor growth xenograft models pre-clinical metastatic estrogen receptor positive (ER+) breast tumor. Decitabine-induced genome-wide DNA hypomethylation results large-scale 3D deregulation, including de-compaction...
Abstract Background Resistance to endocrine therapy is a major clinical challenge in the management of oestrogen receptor (ER)-positive breast cancer. In this setting, p53 frequently wildtype and its activity may be suppressed via upregulation key regulator MDM2. This underlies our rationale evaluate MDM2 inhibition as therapeutic strategy treatment-resistant ER-positive Methods We used inhibitor NVP-CGM097 treat vitro vivo models alone combination with fulvestrant or palbociclib. perform...
Abstract Background Immunotherapy has recently been proposed as a promising treatment to stop breast cancer (BrCa) progression and metastasis. However, there limited success in the of BrCa with immune checkpoint inhibitors. This implies that tumors have other mechanisms escape surveillance. While kynurenine pathway (KP) is known be key player mediating tumor evasion while are several studies on roles KP cancer, little about involvement BrCa. Methods To understand how regulated BrCa, we...
Purpose: Endocrine therapy in combination with CDK4/6 inhibition doubles the progression-free survival of patients advanced ER+ breast cancer, but resistance is inevitable, leaving limited treatment options. Experimental Design: We performed unbiased genome-wide CRISPR/Cas9 knockout screens using cancer cells to identify novel drivers endocrine (tamoxifen) and inhibitor (palbociclib) treatment. Screen hits were validated by models, mechanistic analyses evaluation patient samples. Results:...
<title>Abstract</title> Endocrine therapy in combination with CDK4/6 inhibition doubles the progression-free survival of patients advanced ER + breast cancer, but resistance is inevitable, leaving limited treatment options. Here, we performed unbiased genome-wide CRISPR/Cas9 knockout screens using cancer cells to identify novel drivers endocrine (tamoxifen) and inhibitor (palbociclib) treatment. Our identified inactivation JNK signalling, including loss kinase <italic>MAP2K7</italic>, as a...
The role of androgen receptor (AR) in endocrine-resistant breast cancer is controversial and clinical trials targeting AR with an antagonist (e.g., enzalutamide) have been initiated. Here, we investigated the consequence antagonism using vitro vivo models endocrine resistance. MCF7-derived tamoxifen-resistant (TamR) long-term estrogen-deprived cell lines were achieved siRNA-mediated knockdown or pharmacological inhibition enzalutamide. efficacy enzalutamide was further assessed...
The prediction of breast cancer intrinsic subtypes has been introduced as a valuable strategy to determine patient diagnosis and prognosis, therapy response. PAM50 method, based on the expression levels 50 genes, uses single sample predictor model assign subtype labels samples. Intrinsic errors reported within this assay demonstrate challenge identifying understanding groups. In study, we aim to: a) identify novel biomarkers for individuation by exploring competence newly proposed method...
Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) of metabolites can reveal how metabolism is altered throughout heterogeneous tissues. Here negative ion mode MALDI-MSI has been coupled with post-ionisation (MALDI-2) and applied to the MSI low molecular weight (LMW) (<m/z 600) investigate benefits MALDI-2 offers for spatial metabolomics in terms metabolite coverage sensitivity. When mouse kidney tissue provided almost double number on-tissue specific features...
The estrogen receptor-α (ER-α) is a key driver of breast cancer (BC) and the ER-antagonist, tamoxifen, central pillar BC treatment. However, cross-talk between ER-α, other hormone growth factor receptors enables development de novo resistance to tamoxifen. Herein, we mechanistically dissect activity new class anti-cancer agents that inhibit multiple down-stream signaling for treatment ER-positive BC. Using RNA sequencing comprehensive protein expression analysis, examined...
Despite constituting approximately two thirds of all breast cancers, the luminal A and B tumours are poorly classified at both clinical molecular levels. There contradictory reports on nature these subtypes: some define them as intrinsic entities, others a continuum. With aim addressing uncertainties identifying signatures patients risk, we conducted comprehensive transcriptomic genomic analysis 2,425 cancer samples. Our results indicate that separation between subtypes-per definition-is not...
Multi-gene lists and single sample predictor models have been currently used to reduce the multidimensional complexity of breast cancers, identify intrinsic subtypes. The perceived inability some deal with challenges processing high-dimensional data, however, limits accurate characterisation these Towards development robust strategies, we designed an iterative approach consistently discriminate subtypes improve class prediction in METABRIC dataset.In this study, employed CM1 score most...
Breast cancer is the second most common worldwide and first among women.Invasive ductal carcinoma (IDC) invasive lobular (ILC) are two major histological subtypes, clinical molecular differences between them justify search for new markers to distinguish them.As proteomic analysis allows a powerful analytical approach identify potential biomarkers, we performed comparative of IDC ILC samples by using two-dimensional electrophoresis mass spectrometry.Twenty-three spots were identified...
ABSTRACT Cancer cells invoke phenotypic plasticity programs to drive disease progression and evade chemotherapeutic insults, yet until now there have been no validated clinical therapies targeting this process. Here, we identify a signature associated with poor survival in basal/triple-negative breast cancer, which androgen signalling is prominent. We establish that anti-androgen block cancer stem cell function prevent chemotherapy-induced emergence of new cells. In particular, the agent...
Abstract Three-dimensional (3D) epigenome remodelling is an important mechanism of gene deregulation in cancer. However, its potential as a target to overcome therapy resistance remains largely unaddressed. Here we show that FDA-approved epigenetic Decitabine (5-Aza-mC) suppresses tumour growth preclinical metastatic ER+ breast xenograft models. Decitabine-induced genome-wide DNA hypomethylation results large-scale 3D deregulation, including de-compaction higher order chromatin structure and...
<div>Abstract<p>Resistance to endocrine therapies (ET) is common in estrogen receptor (ER)–positive breast cancer, and most relapsed patients die with ET-resistant disease. Although genetic mutations provide explanations for some relapses, mechanisms of resistance remain undefined many cases. Drug-induced epigenetic reprogramming has been shown possible routes resistance. By analyzing histone H3 lysine 27 acetylation profiles transcriptional models ET resistance, we discovered...
<p>Supplementary Figures</p>