A5052434511- Melanoma and MAPK Pathways
- Brain Metastases and Treatment
- Computational Drug Discovery Methods
- Glioma Diagnosis and Treatment
- Extracellular vesicles in disease
- Nanoplatforms for cancer theranostics
- Cancer Immunotherapy and Biomarkers
- Cutaneous Melanoma Detection and Management
- Cancer Genomics and Diagnostics
- MicroRNA in disease regulation
- Immunotherapy and Immune Responses
- Lung Cancer Research Studies
- Protein Degradation and Inhibitors
- Radiopharmaceutical Chemistry and Applications
- Ocular Oncology and Treatments
- Histone Deacetylase Inhibitors Research
- CAR-T cell therapy research
- Synthesis of Tetrazole Derivatives
- Circular RNAs in diseases
- Neuroblastoma Research and Treatments
- Advanced Breast Cancer Therapies
- Epigenetics and DNA Methylation
- Ferroptosis and cancer prognosis
- Cancer-related molecular mechanisms research
- Spinal Fractures and Fixation Techniques
Melanoma Institute Australia
2013-2025
The University of Sydney
2017-2025
Royal Prince Alfred Hospital
2016-2025
Chris O’Brien Lifehouse
2018-2024
Sydney Hospital
2022
Brainstorm (Spain)
2020
Mater Health Services
2014-2019
Abstract Resistance to immune checkpoint inhibitor therapies in melanoma is common and remains an intractable clinical challenge. In this study, we comprehensively profile resistance mechanisms short-term tumor cell lines matched samples from patients progressing on inhibitors. Combining genome, transcriptome, high dimensional flow cytometric profiling with functional analysis, identify three distinct programs of immunotherapy resistance. Here show that include (1) the loss wild-type antigen...
Exosomes are nano-sized extracellular vesicles released by many cells that contain molecules characteristic of their cell origin, including microRNA. glioblastoma cross the blood-brain barrier into peripheral circulation and carry molecular cargo distinct to "free-circulating" miRNA. In this pilot study, serum exosomal microRNAs were isolated from (n = 12) patients analyzed using unbiased deep sequencing. Results compared sera age- gender-matched healthy controls grade II-III 10) glioma...
Melanoma brain metastasis (MBM) represents a frequent complication of cutaneous melanoma. Despite aggressive multi-modality therapy, patients with MBM often have survival rate <1 year. Alteration in DNA methylation is major hallmark tumor progression and metastasis; however, it remains largely unexplored MBM. In this study, we generated comprehensive landscape through the use genome-wide copy number, gene expression data integrative analysis melanoma to A progressive demethylation low CpG...
The brain is a common site of metastasis for patients with high-risk melanoma. Although surgery or stereotactic radiosurgery are highly effective local treatments small number metastases, there high risk developing additional metastases. role adjuvant whole-brain radiotherapy (WBRT) in reducing new metastases controversial, lack high-level evidence specifically melanoma.In this randomized phase III trial, who had treatment one to three melanoma were randomly assigned WBRT observation....
Abstract Melanoma is a cancer of melanocytes, with multiple subtypes based on body site location. Cutaneous melanoma associated skin exposed to ultraviolet radiation; uveal occurs in the eyes; mucosal internal mucous membranes; and acral palms, soles, nail beds. Here, we present largest whole-genome sequencing study date, 570 tumors profiled, as well methylation RNA for subsets tumors. Uveal genomically distinct from other subtypes, harboring lowest tumor mutation burden significantly...
Abstract Background Biomarkers that reflect glioblastoma tumour activity and treatment response are urgently needed to help guide clinical management, particularly for recurrent disease. As the urinary system is a major clearance route of circulating extracellular vesicles (EVs; 30–1000 nm nanoparticles) we explored whether sampling urinary-EVs could serve as simple non-invasive liquid biopsy approach measuring glioblastoma-associated biomarkers. Methods Fifty urine specimens (15–60 ml) were...
Glioblastoma, WHO-grade IV glioma, carries a dismal prognosis owing to its infiltrative growth and limited treatment options. Glioblastoma-derived extracellular vesicles (EVs; 30-1000 nm membranous particles) influence the microenvironment mediate tumor aggressiveness carry oncogenic cargo across blood-brain barrier into circulation. As such, EVs are biomarker reservoirs with enormous potential for assessing glioblastoma tumors in situ. Neurosurgical aspirates rich sources of EVs, isolated...
The liver is a known site of resistance to immunotherapy and the presence metastases associated with shorter progression-free overall survival (OS) in melanoma, while lung have been more favorable outcome. There are limited data available regarding immune microenvironment at different anatomical sites melanoma metastases. This study sought characterize compare tumor liver, brain, lung, subcutaneous (subcut) as well lymph node (LN) metastases.We analyzed OS 1924 systemic treatment-naïve...
Abstract Background Cerebral metastases are a common cause of death in patients with melanoma. Systemic drug treatment these is rarely effective, and where possible surgical resection and/or stereotactic radiosurgery (SRS) the preferred options. Treatment adjuvant whole brain radiotherapy (WBRT) following neurosurgery SRS controversial. Proponents WBRT report prolongation intracranial control reduced neurological events better palliation. Opponents state melanoma radioresistant; that yields...
Improving outcomes for diffuse glioma patients requires methods that can accurately and sensitively monitor tumour activity treatment response. Extracellular vesicles (EV) are membranous nanoparticles traverse the blood–brain-barrier, carrying oncogenic molecules into circulation. Measuring clinically relevant biomarkers cargoed in circulating EVs could revolutionise how managed. Despite their suitability biomarker discovery, co-isolation of highly abundant complex blood proteins has...
Abstract Glioblastoma (GBM) is an aggressive primary adult brain tumor that rapidly recurs after standard-of-care treatments, including surgery, chemotherapy and radiotherapy. While immune checkpoint inhibitor therapies have transformed outcomes in many types, particularly when used neoadjuvantly or as a first-line treatment, melanoma metastases, they shown limited efficacy patients with resected recurrent GBM. The lack of has been attributed to the scarcity tumor-infiltrating lymphocytes...
Extracellular vesicles (EVs) play key roles in glioblastoma (GBM; astrocytoma grade IV) biology and are novel sources of biomarkers. EVs released from GBM tumors can cross the blood-brain-barrier into periphery carrying molecules, including small non-coding RNA (sncRNA). Biomarkers cargoed circulating have shown great promise for assessing molecular state brain situ. Neurosurgical aspirate fluids captured during tumor resections a rich source GBM-EVs isolated directly microenvironments....
Immunotherapy targeting T-cell inhibitory receptors, namely programmed cell death-1 (PD-1) and/or cytotoxic T-lymphocyte associated protein-4 (CTLA-4), leads to durable responses in a proportion of patients with advanced metastatic melanoma. Combination immunotherapy results higher rates response compared anti-PD-1 monotherapy, at the expense toxicity. Currently, there are no robust molecular biomarkers for selection first-line immunotherapy. We used flow cytometry profile pretreatment tumor...
Four cases previously treated with ipilimumab a total of six histologically confirmed symptomatic lesions RNB without any sign active tumour following stereotactic irradiation MBM are reported. These were all originally thought to be disease recurrence. In two cases, was given prior SRT; in the other after SRT. The average time from first 15 months. SRT 11 diagnosis last follow-up 20 months at which three patients still alive, one no evidence disease. represent approximately percent melanoma...
Summary Historically, the prognosis of patients with melanoma brain metastases is poor, median overall survival ( OS ) 4‐6 months. Little known in era modern systemic therapies and local therapy stereotactic radiosurgery SRS or surgery. Patients diagnosed at Melanoma Institute Australia from January 2011 to December 2014 were included. prognostic factors analysed using Cox regression Kaplan‐Meier analyses.355 The was 7.1 months (95% confidence interval [ CI ] 6.0‐8.1). Median differed by...
Abstract Brain metastases are a major cause of melanoma-related mortality and morbidity. We undertook whole-exome sequencing 50 tumours from patients undergoing surgical resection brain presenting as the first site visceral disease spread validated our findings in an independent dataset 18 patients. had similar driver mutational landscape to cutaneous melanomas TCGA. However, KRAS was most significantly enriched gene, with 4/50 (8%) harbouring non-synonymous mutations. Hotspot mutations were...
Central nervous system (CNS) tumours were one of the first cancer types to adopt and integrate molecular profiling into routine clinical diagnosis in 2016. The vast majority these biomarkers, used discriminate between tumour types, also offered prognostic information. With advent Cancer Genome Atlas (TCGA) other large genomic datasets, further sub-stratification was possible within leading increased precision CNS grading. This review outlines evolution landscape adult tumours, through prism...
Abstract Purpose: This study aimed to identify baseline clinical features associated with the outcomes of patients enrolled in COMBI-MB phase II dabrafenib and trametinib treatment V600 BRAF-mutant metastatic melanoma brain metastases (MBM). Exploratory biomarker analysis was also conducted as part synergistic COMBI-BRV trial (BRV116521), molecular immunologic changes MBMs extracranial (ECM). Patients Methods: Post hoc performed for (n = 125) COMBI-MB. Analyses were intracranial response...
Every year 170,000 patients are diagnosed with brain metastases (BMs) in the United States. Traditionally, adjuvant whole radiotherapy (AWBRT) has been offered following local therapy neurosurgery (NSx) and/or stereotactic radiosurgery (SRS) to BMs. The aim is increase intracranial control, thereby decreasing symptoms from progression and a neurological death. There rapidly evolving change radiation treatment of BMs happening around world. AWBRT now being passed over favour repeat scanning...