A5064190261- Cancer Genomics and Diagnostics
- Cancer-related Molecular Pathways
- Colorectal Cancer Treatments and Studies
- RNA modifications and cancer
- Lung Cancer Treatments and Mutations
- Genetic factors in colorectal cancer
- Cancer Research and Treatments
- Melanoma and MAPK Pathways
- Pancreatic and Hepatic Oncology Research
- Neutropenia and Cancer Infections
- Cancer Treatment and Pharmacology
- Cancer Immunotherapy and Biomarkers
- Peptidase Inhibition and Analysis
- Nutrition, Genetics, and Disease
- Cancer therapeutics and mechanisms
- Gastric Cancer Management and Outcomes
- Cell death mechanisms and regulation
- Cancer, Lipids, and Metabolism
- Cancer Cells and Metastasis
- CAR-T cell therapy research
- Bacterial Identification and Susceptibility Testing
- Molecular Biology Techniques and Applications
- Mathematical Biology Tumor Growth
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
Belfast Health and Social Care Trust
2009-2025
Queen's University Belfast
2009-2024
National Health Service
2018
The Northern Ireland Cancer Centre
2016-2017
University of Ulster
2004-2017
Belfast City Hospital
2004-2017
Cancer Trials Ireland
2015
University of Southern California
2011
Centre for Cancer Biology
2007
Abstract Background Single-agent MEK1/2 inhibition has been disappointing in clinical trials targeting RAS mutant (MT) cancers, probably due to upstream receptor activation, resulting resistance. We previously found that dual c-MET/MEK1/2 attenuated MT colorectal cancer (CRC) xenograft growth. In this study, we assessed safety of inhibitor PD-0325901 with c-MET crizotinib and determined the optimal biological doses for subsequent trials. Methods dose-escalation phase I trial, patients...
Transcriptomic profiling of colorectal cancer (CRC) has led to identification four consensus molecular subtypes (CMS1-4), which have prognostic value in stage II/III disease. More recently, the Colorectal Cancer Intrinsic Subtypes (CRIS) classification system helped define biology specific epithelial component tumors. However, clinical these classifications predicting response standard-of-care adjuvant chemotherapy remains unknown.Using samples from 4 European sites, we assembled a novel CRC...
Immune checkpoint blockade (ICB) has become a standard of care in the treatment recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC). However, only subset patients benefit from treatment. Quantification plasma circulating tumour DNA (ctDNA) levels on-treatment kinetics may permit real-time assessment disease burden under selective pressures treatment.R/M HNSCC treated with systemic therapy, platinum-based chemotherapy (CT) or ICB, underwent serial liquid biopsy sampling....
Abstract Polyamines have been shown to play a role in the growth and survival of several solid tumors, including colorectal cancer. We identified polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT) as being one most highly inducible genes two DNA microarray screens identify novel determinants response chemotherapeutic agents SSAT was be 5-fluorouracil (5-FU) or oxaliplatin parental drug-resistant HCT116 cell lines. It also that mRNA up-regulated 5-FU panel six cancer...
Abstract Chemotherapy response rates for advanced colorectal cancer remain disappointingly low, primarily because of drug resistance, so there is an urgent need to improve current treatment strategies. To identify novel determinants resistance the clinically relevant drugs 5-fluorouracil (5-FU) and SN38 (the active metabolite irinotecan), transcriptional profiling experiments were carried out on pretreatment metastatic biopsies HCT116 parental chemotherapy-resistant cell line models using a...
Abstract Inhibitors of apoptosis proteins (IAPs) are intracellular proteins, with important roles in regulating cell death, inflammation, and immunity. Here, we examined the clinical therapeutic relevance IAPs colorectal cancer. We found that elevated expression cIAP1 cIAP2 (but not XIAP) significantly correlated poor prognosis patients microsatellite stable (MSS) stage III cancer treated 5-fluorouracil (5FU)–based adjuvant chemotherapy, suggesting their involvement promoting...
Background Neutropenic sepsis is a common complication of systemic anticancer treatment. There variation in practice timing switch to oral antibiotics after commencement empirical intravenous antibiotic therapy. Objectives To establish the clinical and cost effectiveness early patients with neutropenic at low risk infective complications. Design A randomised, multicentre, open-label, allocation concealed, non-inferiority trial comparison standard care. Setting Nineteen UK oncology centres....
Significance p53 is the most frequently mutated, well-studied tumor-suppressor gene, yet switch from p53-induced cell-cycle arrest to apoptosis remains poorly understood. We unexpectedly identify a critical role for only human pseudo-caspase FLIP(L) in regulating this switch. Genetically or pharmacologically inhibiting expression of FLIP(L), which we as new transcriptional target, promoted over response activation. Mechanistically, inhibited by blocking ligand-independent activation...
Identifying robust predictive biomarkers to stratify colorectal cancer (CRC) patients based on their response immune-checkpoint therapy is an area of unmet clinical need. Our evolutionary algorithm Atlas Correlation Explorer (ACE) represents a novel approach for mining The Cancer Genome (TCGA) data clinically relevant associations. We deployed ACE identify candidate in CRC. interrogated the colon adenocarcinoma (COAD) gene expression across nine immune-checkpoints (PDL1, PDCD1, CTLA4, LAG3,...
Abstract Background We aimed to assess the safety, tolerability and pharmacokinetics of a novel anti-angiogenic peptide. Methods used an open-label, multicentre, dose-escalation Phase I trial design in patients with solid tumours. ALM201 was administered subcutaneously once daily for 5 days every week unselected Results Twenty (8 male, 12 female) various tumours were treated (18 evaluable toxicity) over eight planned dose levels (10–300 mg). well-tolerated at all without CTCAE grade 4...
Abstract Purpose 5-fluorouracil (5-FU) is inefficiently converted to the active anti-cancer metabolite, fluorodeoxyuridine-monophosphate (FUDR-MP), associated with dose-limiting toxicities and challenging administration schedules. NUC-3373 a phosphoramidate nucleotide analog of fluorodeoxyuridine (FUDR) designed overcome these limitations replace fluoropyrimidines such as 5-FU. Patients methods was administered monotherapy patients advanced solid tumors refractory standard therapy via...
In an attempt to identify genes that are involved in resistance SN38, the active metabolite of irinotecan (also known as CPT-11), we carried out DNA microarray profiling matched HCT116 human colon cancer parental cell lines and SN38-resistant following treatment with SN38 over time.Data analysis identified a list were acutely altered cells well constitutively cells.Independent validation 20% these by quantitative reverse transcription-PCR revealed strong correlation results: Pearson's was...
<h2>Abstract</h2><h3>Objectives</h3> To determine whether early switch to oral antibiotic treatment in adults with neutropenic sepsis at low risk of complications, is non-inferior switching later. <h3>Methods</h3> This non-inferiority, parallel group, randomized, open-label clinical trial enrolled UK hospitalized sepsis. Participants were randomly assigned either ciprofloxacin plus co-amoxiclav within 12-24 hours or continue intravenous for least 48 hours. The primary outcome was a composite...
Src is involved in cancer invasion and metastasis. AZD0424, an oral inhibitor of ABL1, has shown evidence anti-tumour activity pre-clinical studies. A phase Ia, dose escalation study was performed to assess the safety continuous dosing with AZD0424 advanced solid tumours. Secondary objectives included investigation pharmacokinetics, effect on using markers bone turnover, activity. 41 patients were treated; 34 received once-daily at doses ranging from 5 mg 150 mg, 7 40 bi-daily 41.5%...
Despite recent advances in the treatment of both early and advanced colorectal cancer, it remains second leading cause cancer deaths western world. There is, therefore, a pressing need to optimize use currently available systemic therapies identify active new agents for this disease. Pharmacogenomic studies have shown that genetically determined variability key cellular functions can influence toxicity, response survival. Numerous examples these single 'classical' markers been identified...
The topoisomerase I inhibitor irinotecan is used to treat advanced colorectal cancer and has been shown have p53-independent anticancer activity. aim of this study was identify the signaling mechanisms activated by irinotecan. Transcriptional profiling isogenic HCT116 p53 wild-type null cells carried out following treatment with active metabolite irinotecan, SN38. Unsupervised analysis methods showed that status had a highly significant impact on gene expression changes in response Pathway...