A5022826042- Advanced Breast Cancer Therapies
- Cancer-related Molecular Pathways
- Estrogen and related hormone effects
- HER2/EGFR in Cancer Research
- Epigenetics and DNA Methylation
- Cancer Treatment and Pharmacology
- BRCA gene mutations in cancer
- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Chronic Lymphocytic Leukemia Research
- RNA modifications and cancer
- Neuroblastoma Research and Treatments
- Breast Cancer Treatment Studies
- DNA Repair Mechanisms
- Multiple and Secondary Primary Cancers
- Cancer Genomics and Diagnostics
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- Ovarian cancer diagnosis and treatment
- PARP inhibition in cancer therapy
- Signaling Pathways in Disease
- Cell death mechanisms and regulation
Garvan Institute of Medical Research
2018-2025
St Vincent's Clinic
2018-2025
UNSW Sydney
2018-2025
The Kinghorn Cancer Centre
2018-2021
St Vincent's Health
2018
Peter MacCallum Cancer Centre
2018
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...
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...
Genome doubling is an underlying cause of cancer cell aneuploidy and genomic instability, but few drivers have been identified for this process. Due to their physiological roles in the genome reduplication normal cells, we hypothesised that oncogenes cyclins E1 E2 may be cancer. We show both cyclin (CCNE1) (CCNE2) mRNA are significantly associated with high ploidy breast cancers. By live imaging flow cytometry, overexpression promotes aberrant mitosis without causing mitotic slippage, it...
Abstract Basal-like breast cancers (BLBC) are aggressive that respond poorly to targeted therapies and chemotherapies. In order define therapeutically targetable subsets of BLBC we examined two markers: cyclin E1 BRCA1 loss. high grade serous ovarian cancer (HGSOC) these markers mutually exclusive, therapeutic subsets. We tested the same hypothesis for BLBC. Using a cohort enriched loss, identified convergence between loss protein expression, in contrast HGSOC which CCNE1 amplification...
Neuroblastoma is a deadly childhood cancer arising in the developing sympathetic nervous system. High-risk patients are currently treated with intensive chemotherapy, which curative only 50% of children and leaves some surviving life-long side effects. microRNAs (miRNAs) critical regulators neural crest development deregulated during neuroblastoma tumorigenesis, making miRNA-based drugs an attractive therapeutic avenue. A functional screen >1,200 miRNA mimics was conducted cell lines to...
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...
Abstract Background: Selective inhibitors of CDK4/6 kinases (CDK4/6i) were recently FDA approved for use in combination with endocrine therapy (ET), and represent the new standard care. There are however patients who do not respond or develop resistance to these treatments, therapies required this setting. While there is emerging data on mechanisms intrinsic insensitivity CDK4/6i as monotherapies, which include cyclin E1 amplification, CDK6 amplification Rb deletion, little combined ET...
Abstract Resistance to standard-of care-therapies is a significant clinical challenge in estrogen receptor positive (ER+) breast cancer. Cyclin dependent kinase 4/6 inhibitors (CDK4/6i) combination with endocrine therapies (ET) the current standard-of-care for advanced metastatic ER+ cancer; however, resistance this considered inevitable, leading disease progression. The androgen (AR) expressed up 90% of all cancers, and has been associated better patient outcome. Compelling recent...
ABSTRACT Basal-like breast cancers (BLBC) are aggressive that respond poorly to targeted therapies and chemotherapies. In order define therapeutically targetable subsets of BLBC we examined two markers: cyclin E1 BRCA1 loss. high grade serous ovarian cancer (HGSOC) these markers mutually exclusive, therapeutic subsets. We tested the same hypothesis for BLBC. Using a cohort enriched loss, identified convergence between loss expression, in contrast HGSOC which CCNE1 amplification drives...
Abstract Antagonistic sex hormone activity occurs in mammary gland development, whereby estrogen stimulates and androgen inhibits post-pubertal growth, but the mechanistic basis of this is largely unknown. Whether antagonism context breast cancer also unclear. The receptor alpha (ER) unequivocally drives majority malignancies, role (AR) controversial, particularly ER-positive (ER+) tumours resistant to standard-of-care ER targeting therapies. controversy has constrained clinical...
Abstract Background: The Androgen Receptor (AR) is expressed in up to 90% of all ER+ breast cancers and has been associated with better patient outcome. While androgens were used at a high dose as an anticancer therapy historically, this was discontinued the advent Tamoxifen due virilising effects. Non-steroidal, tissue selective AR modulators (SARMs) represent attractive alternative, offering targeted approach activation. Recent compelling pre-clinical data established that tumour...
Searchable abstracts of presentations at key conferences in oncology ISSN 2631-4657 (online)
Searchable abstracts of presentations at key conferences in oncology ISSN 2631-4657 (online)
Searchable abstracts of presentations at key conferences in oncology ISSN 2631-4657 (online)
Abstract Background Resistance to endocrine therapy is a major clinical challenge in the management of estrogen 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 cell...
Abstract Background: Resistance to endocrine therapy is a major clinical challenge in the management of estrogen 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...