A5049781940- Cancer Genomics and Diagnostics
- BRCA gene mutations in cancer
- PARP inhibition in cancer therapy
- Advanced Breast Cancer Therapies
- DNA Repair Mechanisms
- Breast Cancer Treatment Studies
- Genomic variations and chromosomal abnormalities
- Genetic factors in colorectal cancer
- Cancer Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Cancer Treatment and Pharmacology
- Gene expression and cancer classification
- Amino Acid Enzymes and Metabolism
- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- Cancer-related Molecular Pathways
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Cancer Risks and Factors
- Cancer survivorship and care
- Economic and Financial Impacts of Cancer
- Multiple and Secondary Primary Cancers
- COVID-19 and healthcare impacts
- Wnt/β-catenin signaling in development and cancer
- Childhood Cancer Survivors' Quality of Life
University College London
2007-2025
University College London Hospitals NHS Foundation Trust
2017-2025
University College Hospital
2007-2024
CRUK Lung Cancer Centre of Excellence
2023-2024
Cancer Research UK
2002-2023
UCL Biomedical Research Centre
2017-2023
The London College
2021
National Institute for Health Research
2020
Cambridge University Hospitals NHS Foundation Trust
2017-2019
AstraZeneca (United Kingdom)
2018-2019
BackgroundCirculating tumour DNA (ctDNA) testing might provide a current assessment of the genomic profile advanced cancer, without need to repeat biopsy. We aimed assess accuracy ctDNA in breast cancer and ability select patients for mutation-directed therapy.MethodsWe did an open-label, multicohort, phase 2a, platform trial 18 UK hospitals. Participants were women (aged ≥18 years) with histologically confirmed Eastern Cooperative Oncology Group performance status 0–2. Patients had...
Abstract Triple negative breast cancer (TNBC) encompasses molecularly different subgroups, with a subgroup harboring evidence of defective homologous recombination (HR) DNA repair. Here, within phase 2 window clinical trial, RIO trial (EudraCT 2014-003319-12), we investigate the activity PARP inhibitors in 43 patients untreated TNBC. The primary end point, decreased Ki67, occured 12% In secondary point analyses, HR deficiency was identified 69% TNBC mutational-signature-based HRDetect assay....
The cell-cell adhesion receptor gene E-cadherin (CDH1) is expressed by epithelial cells, in which it mediates and morphogenesis. Invasive lobular carcinoma (ILC) characteristically infiltrates diffusely as single cells; immunohistochemistry, many of these tumours lack expression. In the present study we investigated various ways loss function could occur ILCs, namely, promoter methylation, mutation allelic loss. We analysed 22 ILCs found 12 (55%) E-cadherin-negative samples...
Loss of chromosome 18q21 is well documented in colorectal cancer, and it has been suggested that this loss targets the DCC , DPC4 / SMAD4 SMAD2 genes. Recently, importance a downstream regulator TGF-β signaling pathway, cancer highlighted, although frequency mutations appears much lower than loss. We set out to investigate allele loss, mutations, protein expression, cytogenetics 18 copy number collection 44 cell lines known status with respect microsatellite instability (MSI). Fourteen...
Abstract Background: Chromosomal instability (CIN) is thought to be associated with poor prognosis in solid tumors; however, evidence from preclinical and mouse tumor models suggest that CIN may paradoxically enhance or impair cancer cell fitness. Breast prognostic expression signature sets, which reflect status, efficiently delineate outcome estrogen receptor ER-positive breast contrast ER-negative cancer, suggesting the relationship of differs these two subtypes. Methods: Direct assessment...
Abstract Introduction: Subgroups within sporadic triple negative breast cancers (TNBCs) appear to share impaired DNA damage response mechanisms with BRCA1/2 mutation-associated cancers. This has been hypothesised confer particular sensitivity DNA-damaging platinum chemotherapy. The TNT trial, a randomized phase III trial in women metastatic or recurrent locally advanced TNBC cancer, aimed test this hypothesis and examine treatment effect biological subgroups. Patients & Methods: Eligible...
Targeted therapies have yet to significant impact on the survival of patients with bladder cancer. In this study, we focused urea cycle enzyme argininosuccinate synthetase 1 (ASS1) as a therapeutic target in cancer, based our discovery prognostic and functional import ASS1 setting. expression status tumors from 183 Caucasian 295 Asian was analyzed, along its hypothesized association clinicopathologic features, including tumor size invasion. Furthermore, genetics, biology, implications loss...
Abstract The genomics of advanced breast cancer (ABC) has been described through tumour tissue biopsy sequencing, although these approaches are limited by geographical and temporal heterogeneity. Here we use plasma circulating DNA sequencing to interrogate the genomic profile ABC in 800 patients plasmaMATCH trial. We demonstrate diverse subclonal resistance mutations, including enrichment HER2 mutations positive disease, co-occurring ESR1 MAP kinase pathway HR + HER2− disease that associate...
PARTNER is a prospective, phase II-III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer
Abstract In DESTINY-Breast01 (NCT03248492) and DESTINY-Breast03 (NCT03529110), trastuzumab deruxtecan (T-DXd) demonstrated unprecedented activity in patients (pts) with HER2+ (immunohistochemistry 3+; immunohistochemistry 2+/in situ hybridization+) advanced metastatic breast cancer (mBC), leading to regulatory approvals several countries for unresectable/mBC after a prior anti–HER2-based regimen. DESTINY-Breast02 (NCT03523585) is phase 3 trial of T-DXd vs treatment physician’s choice (TPC)...
Abstract Patients with cancer are at increased risk of hospitalisation and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the SARS-CoV-2 phenotype evolution in patients since 2020 has not previously been described. We therefore evaluated on a UK populationscale from 01/11/2020-31/08/2022, assessing case-outcome rates hospital assessment(s), intensive care admission mortality. observed that disease become less non-cancer population....
Abstract Cancers with chromosomal instability (CIN) are held to be aneuploid/polyploid multiple large-scale gains/deletions, but the processes underlying CIN unclear and different types of might exist. We investigated colorectal cancer cell lines using array-comparative genomic hybridization (CGH) for copy number changes single-copy polymorphism (SNP) microarrays allelic loss (LOH). Many array-based CGH were not found by LOH because they did cause true reduction-to-homozygosity. Conversely,...