A5005870582- Melanoma and MAPK Pathways
- Cancer-related Molecular Pathways
- Cancer, Hypoxia, and Metabolism
- Cutaneous Melanoma Detection and Management
- Lung Cancer Treatments and Mutations
- Thyroid Cancer Diagnosis and Treatment
- Cellular Mechanics and Interactions
- Immunotherapy and Immune Responses
- Computational Drug Discovery Methods
- Cell death mechanisms and regulation
- PARP inhibition in cancer therapy
- Hippo pathway signaling and YAP/TAZ
- Cancer Cells and Metastasis
- Cell Adhesion Molecules Research
- Protein Degradation and Inhibitors
- DNA Repair Mechanisms
- S100 Proteins and Annexins
- PI3K/AKT/mTOR signaling in cancer
- Cancer Treatment and Pharmacology
- MRI in cancer diagnosis
- Ovarian cancer diagnosis and treatment
- Multiple Myeloma Research and Treatments
- Chemokine receptors and signaling
- Phagocytosis and Immune Regulation
- Advanced MRI Techniques and Applications
University of Manchester
2011-2024
Wellcome Centre for Cell-Matrix Research
2016
Newcastle University
2011
The ataxia telangiectasia mutated and Rad3-related kinase (ATR) has a key role in the signalling of stalled replication forks DNA damage to cell cycle checkpoints repair. It long been recognised as an important target for cancer therapy but inhibitors have proved elusive. As NU6027, originally developed CDK2 inhibitor, potentiated cisplatin CDK2-independent manner we postulated that it may inhibit ATR. Cellular ATR activity was determined by CHK1 phosphorylation human fibroblasts with...
Despite the general focus on an invasive and de-differentiated phenotype as main driver of cancer metastasis, in melanoma patients many metastatic lesions display a high degree pigmentation, indicative for differentiated phenotype. Indeed, studies mice fish show that cells switch to at secondary sites, possibly because differentiation is closely linked proliferation through lineage-specific transcriptional master regulator MITF. Importantly, while lot effort has gone into identifying factors...
Mitogen-activated protein kinase (MAPK) pathway antagonists induce profound clinical responses in advanced cutaneous melanoma, but complete remissions are frustrated by the development of acquired resistance. Before resistance emerges, adaptive establish a mutation-independent drug tolerance. Antagonizing these could improve effects, thereby thwarting emergence In this study, we reveal that inflammatory niches consisting tumor-associated macrophages and fibroblasts contribute to treatment...
Abstract Approaches to prolong responses BRAF targeting drugs in melanoma patients are challenged by phenotype heterogeneity. Melanomas of a “MITF‐high” usually respond well inhibitor therapy, but these melanomas also contain subpopulations the de novo resistance “AXL‐high” phenotype. > 50% progress with enriched populations, and because AXL is linked de‐differentiation invasiveness avoiding an “AXL‐high relapse” desirable. We discovered that heterogeneity supported during response phase...
Phosphoinositide 3-kinase (PI3K) regulates the transcription factor hypoxia-inducible factor-1 (HIF-1) in thyroid carcinoma cells. Both pathways are associated with aggressive phenotype carcinomas.Our objective was to assess effects of clinical PI3K inhibitor GDC-0941 and genetic inhibition HIF on metastatic behavior cells vitro vivo.Vascular endothelial growth ELISA, activity assays, proliferation studies, scratch-wound migration cell spreading assays were performed under various O(2)...
Abstract The BRAF kinase and the MAPK pathway are targets of current melanoma therapies. However, inhibition results in dynamic changes downstream that can counteract inhibitor‐action not only during treatment, but also acquired resistant tumours. One such change involves expression transcription factor MITF, a crucial regulator cell survival proliferation untreated as well drug‐addicted melanoma. Tight control over MITF levels is required for optimal growth, while it established regulates...
A major challenge for managing melanoma is its tumour heterogeneity based on individual co-existing cell phenotypes. These phenotypes display variable responses to standard therapies, and they drive steps of progression; hence, understanding their behaviour imperative. Melanoma are defined by distinct transcriptional states, which relate different melanocyte lineage development phases, ranging from a mesenchymal, neural crest-like proliferative, melanocytic phenotype. It thought that...
Abstract Background Cervical cancer is the fourth most common in women, with an estimated 342,000 deaths worldwide 2020. Current standard of care UK for locally advanced cervical concurrent chemoradiotherapy weekly cisplatin, yet 5-year overall survival rates are only 65% a distant relapse rate 50%. Inhibitors Apoptosis Proteins (IAPs) often overexpressed cells and associated tumour progression resistance to treatment. Tolinapant, developed by Astex Pharmaceuticals, IAP antagonist additional...
// Natalie Burrows 1, 7 , Joseph Williams 1 Brian A Telfer Julia Resch 2 Helen R Valentine 3 Richard J Fitzmaurice 4 Amanda Eustace Joely Irlam Emily Rowling Cuong Hoang-Vu 5 Catharine M West 3, 6 Georg Brabant Kaye Hypoxia and Therapeutics Group, Manchester Pharmacy School, University of Manchester, UK Experimental Clinical Endocrinology, Medizinische Klinik I, Lubeck, Germany Translational Radiobiology Christie Hospital, NHS Trust, Academic Health Science Centre, Department Histopathology,...
We have developed a non-invasive imaging protocol for dual assessment of hypoxia and glucose uptake in tumours using oxygen-enhanced MRI glucoCESL MRI, test feasibility GL261 glioblastoma MOC2 head neck cancer mouse models. had lower non-perfused fraction (p = 0.0015), trend to higher enhancing 0.07) smaller hypoxic refractory (p= 0.021). The normoxic was significantly larger than the < 0.0001) both These tools will be used assess effects modifying drugs.
Abstract Background: Radiotherapy is used in the treatment of over 50% cancer patients. Although seen as a positive intervention, there are reports radiation enhancing metastatic characteristics cells. We have previously observed that radiotherapy activates number pathways associated with tumour metastases and aggressive phenotype including Src phosphoinositide 3-kinase (PI3K). Here we wished to relate pathway activation cellular investigate impact pharmacological inhibition on response...