Timothy Budden
A5012668221- Ovarian cancer diagnosis and treatment
- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Nonmelanoma Skin Cancer Studies
- Ferroptosis and cancer prognosis
- Cancer Genomics and Diagnostics
- Skin Protection and Aging
- Cutaneous Melanoma Detection and Management
- Cancer Immunotherapy and Biomarkers
- DNA Repair Mechanisms
- Cancer-related molecular mechanisms research
- Cancer Mechanisms and Therapy
- Dermatology and Skin Diseases
- Melanoma and MAPK Pathways
- Cytomegalovirus and herpesvirus research
- Telomeres, Telomerase, and Senescence
- Cytokine Signaling Pathways and Interactions
- Epigenetics and DNA Methylation
- Cancer, Lipids, and Metabolism
- Cell Adhesion Molecules Research
- Animal Virus Infections Studies
- Genomics and Chromatin Dynamics
Cancer Research UK Manchester Institute
2019-2025
University of Manchester
2019-2025
UNSW Sydney
2018-2024
NIHR Manchester Biomedical Research Centre
2021-2023
National Institute for Health Research
2021
Sydney Children's Hospital
2020
University of Newcastle Australia
2013-2018
Hunter Medical Research Institute
2013-2018
Hunter Cancer Research Alliance
2014
Ultraviolet radiation (UVR) damages the dermis and fibroblasts; increases melanoma incidence. Fibroblasts their matrix contribute to cancer, so we studied how UVR modifies dermal fibroblast function, extracellular (ECM) invasion. We confirmed UVR-damaged fibroblasts persistently upregulate collagen-cleaving metalloprotein-1 (MMP1) expression, reducing local collagen (COL1A1), COL1A1 degradation by MMP1 decreased Conversely, inhibiting ECM expression restored Primary cutaneous melanomas of...
Abstract Purpose: Gene expression–based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation clinical utility has been hindered by nonstandardized methods, which are not applicable in a setting. We sought to generate grade minimal gene set assay classification individual tumor specimens into HGSOC and confirm previously reported subtype-associated...
// Timothy Budden 1 , Ryan J. Davey Ricardo E. Vilain 1,2,3,4 Katie A. Ashton Stephen G. Braye 4 Natalie Beveridge and Nikola Bowden Hunter Medical Research Institute Faculty of Health, University Newcastle, Callaghan, NSW, Australia 2 Melanoma Australia, Camperdown, 3 Sydney School, Sydney, Area Pathology Service, North, John Hospital, Correspondence to: Bowden, email: Keywords : melanoma, UVB, global genome repair, XPC, nucleotide excision repair Received July 02, 2016 Accepted 14,...
Abstract Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes how co-occurrence BRCA1 or BRCA2 (BRCA) alterations loss influences in tubo-ovarian high-grade serous (HGSC). Experimental Design: protein classified by immunohistochemistry carcinomas 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined germline BRCA status a subset 1,134 HGSC, related genotype overall (OS), tumor-infiltrating CD8+ lymphocytes,...
KRASG12C and KRASG12D inhibitors represent a major translational breakthrough for non-small cell lung cancer (NSCLC) in general by directly targeting its most mutated oncoprotein. However, resistance to these small molecules has highlighted the need rational combination partners necessitating critical understanding of signaling downstream KRAS mutant isoforms. We contrasted tumor development between KrasG12C KrasG12D genetically engineered mouse models (GEMMs). To corroborate findings...
Many cancer types display sex and age disparity in incidence outcome. The mutational load of tumours, including melanoma, varies according to age. However, there are no tools explore systematically whether clinical variables such as determine the genomic landscape cancer.To establish a mathematical approach using melanoma data analyse how shape tumour genome.We model age-related (clock-like) somatic mutations that arise during cell division, extrinsic (environmental ultraviolet radiation)...
Melanoma has two key features, an over-representation of UV-induced mutations and resistance to DNA damaging chemotherapy agents. Both these features may result from dysfunction the nucleotide excision repair pathway, in particular damage detection branch, global genome (GGR). The GGR component XPC does not respond melanoma, cause this lack response been investigated. In study, we investigated role methylation reduced melanoma. To reduce induce DNA-damage, melanoma cell lines were treated...
Cancer susceptibility and mortality are higher in males, the mutational transcriptomic landscape of cancer differs by sex. The current assumption is that men at risk epithelial cancers as they expose more to carcinogens accumulate damage than women. We present data showing women with less aggressive primary cutaneous squamous cell carcinoma (cSCC) early strong immune activation.We explored clinical molecular sexual disparity immunocompetent immunosuppressed patients cSCC (N = 738, N 160),...
ObjectiveAdvanced stage mucinous ovarian cancers are diagnostically and therapeutically challenging. Histotype specific trials have failed due to low recruitment after excluding non-ovarian primaries. Mucinous commonly metastatic from other sites however lack definitive diagnostic markers. We suggest a classification of uncertain primary origin ‘MO-CUPs’ in clinical trials. This study aims identify drug targets guide treatment future trials.MethodsWe analyzed large de-identified,...
Nucleotide excision repair (NER) orchestrates the of helix distorting DNA damage, induced by both ultraviolet radiation (UVR) and cisplatin. There is evidence that global genome (GGR) arm NER dysfunctional in melanoma it known to have limited induction cell lines after cisplatin treatment. The aims this study were examine mRNA transcript levels regulators GGR investigate downstream effect on expression treatment tumours. regulators, BRCA1 PCNA, melanocytes cisplatin, but not lines....
Melanocortin 1 receptor (MC1R) is a G protein-coupled expressed in melanocytes where it plays an important role skin pigmentation and the UV response, has implications melanoma development. Here we show that methylation of CpG island (CGI) within MC1R gene can control expression melanoma. This CGI overlaps with potential enhancer region, unmethylated normal but highly methylated other cells, suggesting melanocyte specific function. Analysis showed was only significantly differentially by...
Abstract Direct inhibitors of KRASG12C and more recently KRASG12D are currently under clinical evaluation may represent the beginning a major translational breakthrough for non-small cell lung cancer (NSCLC) RAS addicted cancers in general, targeting most commonly mutated oncogene this disease. However early reports resistance with inactive state-selective have highlighted pressing need rational combination partners. While preclinical strategies to enhance inhibition combat innate already...
<p>Expression of RB1 and survival associations across ovarian cancer histotypes. <b>A,</b> Representative images IHC detection expression in carcinoma tissues, showing examples the three most common patterns: retained, lost, subclonal loss. <b>B,</b> Proportion patients with loss or retention protein tumor samples by <i>χ</i><sup>2</sup><i>P</i> value reported for difference proportions all CCOC, clear cell cancer; LGSC,...
<p>Supplementary Figure S10. Immune cell subsets inferred from gene expression data by combined homologous recombination deficiency and RB1 status.</p>
<p>Supplementary Figure S5. Cell proliferation and cell cycle distribution of HGSC lines with RB1 knockout.</p>
<div>AbstractPurpose:<p>The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes how co-occurrence <i>BRCA1</i> or <i>BRCA2</i> (<i>BRCA</i>) alterations loss influences in tubo-ovarian high-grade serous (HGSC).</p>Experimental Design:<p>RB1 protein classified by immunohistochemistry carcinomas 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined germline...
<p>Supplementary Figure S2. Representative immunohistochemical RB1 staining patterns.</p>
<p>Supplementary Figure S10. Immune cell subsets inferred from gene expression data by combined homologous recombination deficiency and RB1 status.</p>
<p>Supplementary Figure S5. Cell proliferation and cell cycle distribution of HGSC lines with RB1 knockout.</p>
<p>Sensitivity to therapeutic agents in <i>BRCA1</i>-altered cell lines with <i>RB1</i> knockout. <b>A,</b><i>RB1</i> was knocked out using CRISPR/Cas9 three patient-derived Australian Ovarian Cancer Study (AOCS) HGSC either wild-type or altered <i>BRCA1</i> (<i>BRCA1</i> var) background. Representative Western Blots show protein levels of RB1 and phosphorylated (pRB1) compared GAPDH loading control single-cell...