A5102008707- Cancer Cells and Metastasis
- Lung Cancer Research Studies
- Cancer, Hypoxia, and Metabolism
- Cancer Genomics and Diagnostics
- Neuroendocrine Tumor Research Advances
- Amino Acid Enzymes and Metabolism
- Metabolism, Diabetes, and Cancer
- Pancreatic and Hepatic Oncology Research
- Lung Cancer Treatments and Mutations
- Acute Myeloid Leukemia Research
- Colorectal Cancer Treatments and Studies
- Retinoids in leukemia and cellular processes
- Colorectal Cancer Surgical Treatments
- Radiomics and Machine Learning in Medical Imaging
- Cancer, Lipids, and Metabolism
- Prostate Cancer Treatment and Research
- Cancer Research and Treatments
- Metastasis and carcinoma case studies
- Innovative Microfluidic and Catalytic Techniques Innovation
- Occupational and environmental lung diseases
- Radio Frequency Integrated Circuit Design
- Gallbladder and Bile Duct Disorders
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Statistical Methods in Clinical Trials
- Gastric Cancer Management and Outcomes
Cancer Research UK Manchester Institute
2013-2023
Cancer Genetics (United States)
2018-2022
National Cancer Institute
2018-2022
Leidos (United States)
2018-2022
Frederick National Laboratory for Cancer Research
2018-2022
University of Manchester
2004-2021
CRUK Lung Cancer Centre of Excellence
2016
Cancer Research UK
2016
National Health Service
2012
Purpose Circulating tumor cells (CTCs) may have utility as surrogate biomarkers and “virtual” biopsies. We report the clinical significance molecular characteristics of CTCs CTC clusters, termed circulating microemboli (CTM), detected in patients with small-cell lung cancer (SCLC) undergoing standard treatment. Patients Methods Serial blood samples from 97 receiving chemotherapy were analyzed using EpCam-based immunomagnetic detection a filtration-based technique. Proliferation status (Ki67)...
Inhibition of monocarboxylate transporter (MCT) 1-mediated lactate transport may have cytostatic and/or cytotoxic effects on tumor cells. We report results from the dose-escalation part a first-in-human trial AZD3965, first-in-class MCT1 inhibitor, in advanced cancer.
Although nonmalignant stromal cells facilitate tumor growth and can occupy up to 90% of a solid mass, better strategies exploit these for improved cancer therapy are needed. Here, we describe potent MMAE-linked antibody-drug conjugate (ADC) targeting endothelial marker 8 (TEM8, also known as ANTXR1), highly conserved transmembrane receptor broadly overexpressed on cancer-associated fibroblasts, endothelium, pericytes. Anti-TEM8 ADC elicited anticancer activity through an unexpected killing...
Tumor recurrence after surgical resection of NSCLC obstructs long-term disease-free survival in approximately 50% cases. Our data suggest that combining circulating tumor cell enumeration (as single cells or clusters) tumor-draining pulmonary vein and peripheral blood (assessed by CellSearch) at the time surgery better identifies those patients higher risk for lung cancer than does number alone.
Small cell lung cancer (SCLC) is a neuroendocrine characterized by fast growth, early dissemination, and rapid resistance to chemotherapy. We identified population of long-term tumor-propagating cells (TPCs) in mouse model SCLC. This population, marked high levels EpCAM CD24, also prevalent human primary SCLC tumors. Murine TPCs are numerous highly proliferative but not intrinsically chemoresistant, indicating that all clinical features linked TPCs. possess distinct transcriptional profile...
BackgroundThe clinical significance of circulating tumour cells (CTCs) in limited-stage small-cell lung cancer (LS-SCLC) is not well defined. We report a planned exploratory analysis the prevalence and prognostic value CTCs LS-SCLC patients enrolled within phase III randomised CONVERT (concurrent once-daily versus twice-daily chemoradiotherapy) trial.Patients methodsBaseline blood samples were enumerated for using CellSearch 75 with who trial between twice- concurrent chemoradiation....
Collagen I, the most abundant protein in humans, is ubiquitous solid tumors where it provides a rich source of exploitable metabolic fuel for cancer cells. While tumor cells were unable to exploit collagen directly, here we show they can usurp byproducts collagen-consuming tumor-associated stroma. Using genetically engineered mouse models, discovered that growth depends upon binding and uptake mediated by TEM8/ANTXR1 cell surface Tumor-associated stromal processed into glutamine, which was...
The detection and enumeration of circulating tumor cells (CTCs) has shown significant clinical utility with respect to prognosis in breast, colorectal prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information aid therapy decision making. as a ‘virtual real-time biopsy’ have clear potential facilitate exploration biology, particular, the process metastasis. challenge profiling CTC molecular characteristics generating signatures using current technologies is...
Circulating tumour cells (CTC) are receiving increasing attention as prognostic, predictive and pharmacodynamic biomarkers in cancer patients. However, their clinical significance can be dependent on an accurate determination of CTC around cut-off values at low cell counts (<10 cells/7.5 ml). Consequently, we have conducted method validation the CellSearch™ system focusing samples containing region. Analytical accuracy was first assessed employing quality controls (QC) spiked healthy...
AZD3514 inhibits and down regulates the androgen receptor (AR) has undergone clinical trials in prostate cancer. To provide proof-of-mechanism (POM) patients, an immunohistochemistry (IHC) method for determination of AR circulating tumour cells (CTC) was developed validated. After assessment specificity validation focused on intra- inter-operator reproducibility utilising a novel modification incurred sample reanalysis (ISR). β-Content γ-confidence tolerance intervals (BCTI) Cohen's Kappa...
Given the current postulated plasticity between epithelial and mesenchymal states of migratory cancer cells detection non-epithelial CTCs is an important scientific clinical goal.We used filtration-based ISET technology to enrich circulating tumour (CTCs) in early breast blood samples identify them using a morphology-based immunocytochemistry (ICC) approach.We found greater numbers putative by this approach than cytokeratin-based CellSearch technology, but high number CTC false positives...
The monocarboxylate transporter-1 (MCT1) represents a novel target in rational anticancer drug design while AZD3965 was developed as an inhibitor of this transporter and is undergoing Phase I clinical trials ( http://www.clinicaltrials.gov/show/NCT01791595 ). We describe the optimisation immunofluorescence (IF) method for determination MCT1 MCT4 circulating tumour cells (CTC) potential prognostic predictive biomarkers cancer patients. Antibody selectivity investigated by western blotting...
Abstract Background Patients with metastatic colorectal cancer are treated cytotoxic chemotherapy supplemented by molecularly targeted therapies. There is a critical need to define biomarkers that can optimise the use of these therapies maximise efficacy and avoid unnecessary toxicity. However, it important first changes in potential following alone. This study reports impact standard across range circulating imaging biomarkers. Methods A single-centre, prospective, biomarker-driven study....
107 Background: Saracatinib is an orally-available, highly selective inhibitor of Abl and Src family members. It ATP-competitive tyrosine kinase inhibitor. Preclinical data suggested that the combination a docetaxel synergistic, activity was also implicated in bone’s metabolic response to cancer metastases. Methods: Patients with mCRPC were initially enrolled open-label, dose escalation phase I trial oral saracatinib (cohorts 50mg, 125mg 175mg daily) (75mg/m 2 ) 3+3 design. Subsequent...
Abstract Small cell lung cancer (SCLC), is a highly aggressive and metastatic disease with 5 year survival of 5%. SCLC represents 15-20% all cancers causes &gt;160,000 deaths year. The majority patients present consequently resections are rare, while biopsies small only for diagnostic purposes thus hampering the study SCLC. However, circulating tumour cells (CTCs) prevalent in may represent an avenue better understanding this disease. Our aim was to determine whether CTCs isolated from...