A5101707847- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Renal cell carcinoma treatment
- Lung Cancer Treatments and Mutations
- Cancer Immunotherapy and Biomarkers
- Gastric Cancer Management and Outcomes
- Protein Degradation and Inhibitors
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Esophageal Cancer Research and Treatment
- Renal and related cancers
- Radiomics and Machine Learning in Medical Imaging
- Pancreatic and Hepatic Oncology Research
- Ferroptosis and cancer prognosis
- Mathematical Biology Tumor Growth
- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
- Microtubule and mitosis dynamics
- Colorectal and Anal Carcinomas
- CAR-T cell therapy research
- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
St Bartholomew's Hospital
2008-2025
Queen Mary University of London
2010-2025
Barts Health NHS Trust
2012-2025
Royal Marsden NHS Foundation Trust
2014-2024
Institute of Cancer Research
2014-2023
Hôpital Européen Georges-Pompidou
2023
Royal Marsden Hospital
2014-2022
Institute of Cancer Research
2018-2022
University of Chicago
2019
Cancer Research UK
2010-2017
Intratumor heterogeneity may foster tumor evolution and adaptation hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples.
Spatial and temporal dissection of the genomic changes occurring during evolution human non-small cell lung cancer (NSCLC) may help elucidate basis for its dismal prognosis. We sequenced 25 spatially distinct regions from seven operable NSCLCs found evidence branched evolution, with driver mutations arising before after subclonal diversification. There was pronounced intratumor heterogeneity in copy number alterations, translocations, associated APOBEC cytidine deaminase activity. Despite...
Most advanced solid tumors remain incurable, with resistance to chemotherapeutics and targeted therapies a common cause of poor clinical outcome. Intratumor heterogeneity may contribute this failure by initiating phenotypic diversity enabling drug emerge introducing tumor sampling bias. Envisaging growth as Darwinian tree the trunk representing ubiquitous mutations branches heterogeneous help in discovery development predictive biomarkers response.
Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRCs). This genomic and transcriptomic analysis resistance landscape in 35 RAS wild-type CRCs identified associations NF1 non-canonical RAS/RAF aberrations with primary validated CRC subtypes as non-genetic predictors benefit. Sixty-four percent biopsies acquired harbored no genetic drivers. Most these had switched from cetuximab-sensitive subtype at baseline to...
Defining mechanisms that generate intratumour heterogeneity and branched evolution may inspire novel therapeutic approaches to limit tumour diversity adaptation. SETD2 (Su(var), Enhancer of zeste, Trithorax-domain containing 2) trimethylates histone-3 lysine-36 (H3K36me3) at sites active transcription is mutated in diverse types, including clear cell renal carcinomas (ccRCCs). Distinct mutations have been identified spatially separated regions ccRCC, indicative heterogeneity. In this study,...
Candidate biomarkers have been identified for clear cell renal carcinoma (ccRCC) patients, but most not validated.
Addition of taxanes to preoperative chemotherapy in breast cancer increases the proportion patients who have a pathological complete response (pCR). However, substantial do not respond, and prognosis is particularly poor for with oestrogen-receptor (ER)/progesterone-receptor (PR)/human epidermal growth factor receptor 2 (HER2; ERBB2)-negative (triple-negative) disease achieve pCR. Reliable identification such first step determining might benefit from alternative treatment regimens clinical...
<h3>Background</h3> Patient derived organoids (PDOs) can be established from colorectal cancers (CRCs) as in vitro models to interrogate cancer biology and its clinical relevance. We applied mass spectrometry (MS) immunopeptidomics investigate neoantigen presentation whether this augmented through interferon gamma (IFNγ) or MEK-inhibitor treatment. <h3>Methods</h3> Four microsatellite stable PDOs chemotherapy refractory one a treatment naïve CRC were expanded replicates with 100 million...
<h3>Background</h3> The T cell bispecific antibody cibisatamab (CEA-TCB) binds Carcino-Embryonic Antigen (CEA) on cancer cells and CD3 cells, which triggers killing of lines expressing moderate to high levels CEA at the surface. Patient derived colorectal organoids (PDOs) may more accurately represent patient tumors than established potentially enables detailed insights into mechanisms resistance sensitivity. <h3>Methods</h3> We PDOs from multidrug-resistant metastatic CRCs. expression was...
Abstract The application of evolutionary and ecological principles to cancer prevention treatment, as well recognizing a selection force in nature, has gained impetus over the last 50 years. Following initial theoretical approaches that combined knowledge from interdisciplinary fields, it became clear using eco‐evolutionary framework is key importance understand cancer. We are now at pivotal point where accumulating evidence starts steer future directions discipline allows us underpin...
The recognition of cancer cells by T can impact upon prognosis and be exploited for immunotherapeutic approaches. This depends on the specific interaction between antigens displayed surface cell receptor (TCR), which is generated somatic rearrangements TCR α- β-chains (TCRb). Our aim was to assess whether ultra-deep sequencing rearranged TCRb in DNA extracted from unfractionated clear renal carcinoma (ccRCC) samples provide insights into clonality heterogeneity intratumoural ccRCCs, a tumour...
Intratumour heterogeneity (ITH) may foster tumour adaptation and compromise the efficacy of personalized medicine approaches. The scale within a (intratumour heterogeneity) relative to genetic differences between tumours (intertumour is unknown. To address this, we obtained 48 biopsies from eight stage III IV clear cell renal carcinomas (ccRCCs) used DNA copy-number analyses compare same with 440 single Cancer Genome Atlas (TCGA). Unsupervised hierarchical clustering TCGA multi-region ccRCC...
Background10%–15% of early-stage colon cancers harbour either deficient mismatch repair (dMMR), microsatellite instability high (MSI-H) or POLE exonuclease domain mutations, and are characterised by tumour mutational burden increased lymphocytic infiltrate. Metastatic dMMR highly sensitive to immune checkpoint inhibition, recent data show POLE-mutant tumours similarly responsive. We conducting a phase III randomised trial determine if the addition anti-PD-L1 antibody avelumab following...
Mismatch repair deficient (dMMR) gastro-oesophageal adenocarcinomas (GOAs) show better outcomes than their MMR-proficient counterparts and high immunotherapy sensitivity. The hypermutator-phenotype of dMMR tumours theoretically enables evolvability but evolution has not been investigated. Here we apply multi-region exome sequencing (MSeq) to four treatment-naive GOAs. This reveals extreme intratumour heterogeneity (ITH), exceeding ITH in other cancer types >20-fold, also long phylogenetic...
The gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map CRC mucosal and metabolome define influence tumoral on oncological outcomes.A multicentre, prospective observational study was conducted patients undergoing primary surgical resection UK (n = 74) Czech Republic 61). Analysis performed using metataxonomics, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), targeted bacterial qPCR tumour exome sequencing. Hierarchical clustering...