Andrew Rowan
A5056141826- Cancer Genomics and Diagnostics
- Animal testing and alternatives
- Human-Animal Interaction Studies
- Renal cell carcinoma treatment
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Animal Behavior and Welfare Studies
- DNA Repair Mechanisms
- Melanoma and MAPK Pathways
- Wildlife Ecology and Conservation
- Cutaneous Melanoma Detection and Management
- Cancer Immunotherapy and Biomarkers
- Zoonotic diseases and public health
- Geographies of human-animal interactions
- Lung Cancer Treatments and Mutations
- Veterinary Pharmacology and Anesthesia
- Computational Drug Discovery Methods
- Rabies epidemiology and control
- Animal and Plant Science Education
- Genetic factors in colorectal cancer
- Renal and related cancers
- Agriculture Sustainability and Environmental Impact
- Cell Image Analysis Techniques
- Immunotherapy and Immune Responses
- Esophageal Cancer Research and Treatment
The Francis Crick Institute
2016-2025
University College London
2017-2023
London Cancer
2017-2023
University College London Hospitals NHS Foundation Trust
2020
National Hospital for Neurology and Neurosurgery
2020
Humane Society of the United States
2006-2019
University of the Potomac
2019
Cancer Institute (WIA)
2017
CRUK Lung Cancer Centre of Excellence
2017
The Honourable Society of Lincoln's Inn
2000-2015
Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and genome evolution have been limited to small retrospective cohorts. We wanted prospectively investigate in relation clinical outcome determine the clonal nature of driver events evolutionary processes early-stage NSCLC.
Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, polymorphic nature locus has precluded accurate HLA copy-number analysis. Here, we heterozygosity in (LOHHLA), computational tool determine allele-specific copy number from sequencing data. Using LOHHLA, find that LOH occurs 40% non-small-cell lung cancers (NSCLCs) and associated with high subclonal neoantigen burden,...
The focus of tumour-specific antigen analyses has been on single nucleotide variants (SNVs), with the contribution small insertions and deletions (indels) less well characterised. We investigated whether frameshift nature indel mutations, which create novel open reading frames a large quantity mutagenic peptides highly distinct from self, might contribute to immunogenic phenotype.
Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 biopsies across 100 patients with ccRCC, including two cases sampledat post-mortem. Metastatic competence was afforded by chromosome complexity, identify 9p loss as highly selected event driving metastasis ccRCC-related mortality (p = 0.0014). Distinct patterns dissemination were observed, rapid progression multiple...
The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. observe up 30 driver events per and show that subclonal diversification is associated with known prognostic parameters. By resolving patterns event ordering, co-occurrence, mutual exclusivity at clone level, we deterministic nature clonal evolution. ccRCC...
Clear cell renal carcinoma (ccRCC) is characterized by near-universal loss of the short arm chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear carcinoma. find hotspots point mutations in 5′ UTR TERT, targeting a MYC-MAX-MAD1 repressor associated telomere lengthening. The most common structural abnormality generates simultaneous 3p and 5q gain (36% patients), typically through chromothripsis. This event occurs...
Metastases undergo reconstruction Cancer cells from primary tumors can migrate to regional lymph nodes and distant organs. The prevailing model in oncology is that node metastases give rise metastases. This “sequential progression model” the rationale for surgical removal of tumor-draining nodes. Naxerova et al. used phylogenetic methods reconstruct evolutionary relationship tumors, metastases, 17 patients with colorectal cancer (see Perspective by Markowitz). sequential applied only...
CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that expression largely restricted to tumor-infiltrating Treg in mice humans. While existing were observed deplete the periphery, upregulation of inhibitory Fc gamma receptor (FcγR) IIb tumor site prevented intra-tumoral cell depletion, which may underlie lack...
Esophageal adenocarcinomas are associated with a dismal prognosis. Deciphering the evolutionary history of this disease may shed light on therapeutically tractable targets and reveal dynamic mutational processes during course following neoadjuvant chemotherapy (NAC). We exome sequenced 40 tumor regions from 8 patients operable esophageal adenocarcinomas, before after platinum-containing NAC. This revealed genomic landscape presence heterogeneous driver mutations, parallel evolution, early...
TRACERx, a prospective study of patients with primary non-small cell lung cancer, aims to map the genomic landscape cancer by tracking clonal heterogeneity and tumour evolution from diagnosis relapse.
ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates clinical T receptor (TCR) analysis reveals significantly higher number expanded TCR...
Abstract B cells are frequently found in the margins of solid tumours as organized follicles ectopic lymphoid organs called tertiary structures (TLS) 1,2 . Although TLS have been to correlate with improved patient survival and response immune checkpoint blockade (ICB), underlying mechanisms this association remain elusive Here we investigate lung-resident cell responses patients from TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) other lung cancer cohorts, a...
Metastatic disease is responsible for the majority of cancer-related deaths
Abstract Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance therapy 1 . Here, using paired whole-exome RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell tumours from 347 out of the first 421 patients prospectively recruited into TRACERx study 2,3 Analyses 947 tumour regions, representing both primary metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate transcriptome...
Abstract In this study, the impact of apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell (NSCLC) mouse models constrained tumorigenesis, while tumors treated with EGFR-targeted therapy associated treatment resistance. Analyses human NSCLC showed upregulation and revealed therapy-induced activation nuclear kappa (NF-κB) as an...
Background Understanding the cancer genome is seen as a key step in improving outcomes for patients. Genomic assays are emerging possible avenue to personalised medicine breast cancer. However, evolution of during natural history largely unknown, profile disease at death. We sought study detail these aspects advanced cancers that have resulted lethal disease. Methods and Findings Three patients with oestrogen-receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative...
Abstract Papillary renal cell carcinoma (pRCC) is an important subtype of kidney cancer with a problematic pathological classification and highly variable clinical behaviour. Here we sequence the genomes or exomes 31 pRCCs, in four tumours, multi-region sequencing undertaken. We identify BAP1 , SETD2 ARID2 Nrf2 pathway genes ( KEAP1 NHE2L2 CUL3 ) as probable drivers, together at least eight other possible drivers. However, only ~10% tumours harbour detectable pathogenic changes any one...
Abstract Intercellular heterogeneity, exacerbated by chromosomal instability (CIN), fosters tumor heterogeneity and drug resistance. However, extreme CIN correlates with improved cancer outcome, suggesting that karyotypic diversity required to adapt selection pressures might be balanced in tumors against the risk of excessive instability. Here, we used a functional genomics screen, genome editing, pharmacologic approaches identify CIN-survival factors diploid cells. We find partial...