Alan Serrels
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View article: Tumour genotype shapes blood biomarker expression for use in pancreatic cancer detection and diagnosis
Tumour genotype shapes blood biomarker expression for use in pancreatic cancer detection and diagnosis Open
Typically diagnosed late, when systemic metastasis has already occurred, pancreatic ductal adenocarcinoma (PDAC) has one of the worst 5-year survival rates of any cancer type. For many patients with advanced disease, current chemotherapy r…
View article: Exploring BenzylethoxyAryl Urea Scaffolds for Multitarget Immunomodulation Therapies
Exploring BenzylethoxyAryl Urea Scaffolds for Multitarget Immunomodulation Therapies Open
Thirteen benzylethoxyaryl ureas have been synthesized and biologically evaluated as multitarget inhibitors of VEGFR-2 and PD-L1 proteins to overcome resistance phenomena offered by cancer. The antiproliferative activity of these molecules …
View article: FAK suppresses antigen processing and presentation to promote immune evasion in pancreatic cancer
FAK suppresses antigen processing and presentation to promote immune evasion in pancreatic cancer Open
Objective Immunotherapy for the treatment of pancreatic ductal adenocarcinoma (PDAC) has shown limited efficacy. Poor CD8 T-cell infiltration, low neoantigen load and a highly immunosuppressive tumour microenvironment contribute to this la…
View article: 11β-HSD1 inhibition does not affect murine tumour angiogenesis but may exert a selective effect on tumour growth by modulating inflammation and fibrosis
11β-HSD1 inhibition does not affect murine tumour angiogenesis but may exert a selective effect on tumour growth by modulating inflammation and fibrosis Open
Glucocorticoids inhibit angiogenesis by activating the glucocorticoid receptor. Inhibition of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) reduces tissue-specific glucocorticoid action and promote…
View article: Kindlin-1 regulates IL-6 secretion and modulates the immune environment in breast cancer models
Kindlin-1 regulates IL-6 secretion and modulates the immune environment in breast cancer models Open
The adhesion protein Kindlin-1 is over-expressed in breast cancer where it is associated with metastasis-free survival; however, the mechanisms involved are poorly understood. Here, we report that Kindlin-1 promotes anti-tumor immune evasi…
View article: ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning
ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning Open
Precise vascular patterning is crucial for normal growth and development. The ERG transcription factor drives Delta-like ligand 4 (DLL4)/Notch signalling and is thought to act as a pivotal regulator of endothelial cell (EC) dynamics and de…
View article: Loss of the adhesion protein Kindlin-1 stimulates tumor clearance via modulation of Tregs
Loss of the adhesion protein Kindlin-1 stimulates tumor clearance via modulation of Tregs Open
The adhesion protein Kindlin-1 is over-expressed in breast cancer where it has been shown to be associated with metastasis-free survival, however, the mechanisms involved are poorly understood. Here, we report that Kindlin-1 promotes anti-…
View article: 11β-HSD1 inhibition does not affect murine tumour angiogenesis but may exert a selective effect on tumour growth by modulating inflammation and fibrosis
11β-HSD1 inhibition does not affect murine tumour angiogenesis but may exert a selective effect on tumour growth by modulating inflammation and fibrosis Open
Glucocorticoids inhibit angiogenesis by activating the glucocorticoid receptor. Inhibition of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) reduces tissue-specific glucocorticoid action and promote…
View article: T-cell co-stimulation in combination with targeting FAK drives enhanced anti-tumor immunity
T-cell co-stimulation in combination with targeting FAK drives enhanced anti-tumor immunity Open
Focal Adhesion Kinase (FAK) inhibitors are currently undergoing clinical testing in combination with anti-PD-1 immune checkpoint inhibitors. However, which patients are most likely to benefit from FAK inhibitors, and what the optimal FAK/i…
View article: Author response: T-cell co-stimulation in combination with targeting FAK drives enhanced anti-tumor immunity
Author response: T-cell co-stimulation in combination with targeting FAK drives enhanced anti-tumor immunity Open
Article Figures and data Abstract Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract Focal Adhesion Kinase (FAK) inhibitors are…
View article: Exposure to the antimicrobial peptide LL-37 produces dendritic cells optimized for immunotherapy
Exposure to the antimicrobial peptide LL-37 produces dendritic cells optimized for immunotherapy Open
Immunization of patients with autologous, ex vivo matured dendritic cell (DC) preparations, in order to prime antitumor T-cell responses, is the focus of intense research. Despite progress and approval of clinical approaches, significant e…
View article: Development of a fluorescence-based cellular apoptosis reporter
Development of a fluorescence-based cellular apoptosis reporter Open
Evasion of apoptosis is a hallmark of human cancer, and a desired endpoint of many anticancer agents is the induction of cell death. With the heterogeneity of cancer becoming increasingly apparent, to understand drug mechanisms of action a…
View article: High-Precision Photothermal Ablation Using Biocompatible Palladium Nanoparticles and Laser Scanning Microscopy
High-Precision Photothermal Ablation Using Biocompatible Palladium Nanoparticles and Laser Scanning Microscopy Open
Herein, we report a straightforward method for the scalable preparation of Pd nanoparticles (Pd-NPs) with reduced inherent cytotoxicity and high photothermal conversion capacity. These Pd-NPs are rapidly taken up by cells and able to kill …
View article: IL-33 and ST2 mediate FAK-dependent antitumor immune evasion through transcriptional networks
IL-33 and ST2 mediate FAK-dependent antitumor immune evasion through transcriptional networks Open
The kinase FAK coordinates chromatin modifiers and transcription factors to orchestrate evasion of antitumor immune responses.
View article: Nuclear FAK and Runx1 Cooperate to Regulate IGFBP3, Cell-Cycle Progression, and Tumor Growth
Nuclear FAK and Runx1 Cooperate to Regulate IGFBP3, Cell-Cycle Progression, and Tumor Growth Open
Nuclear focal adhesion kinase (FAK) is a potentially important regulator of gene expression in cancer, impacting both cellular function and the composition of the surrounding tumor microenvironment. Here, we report in a murine model of ski…
View article: FAK-inhibition opens the door to checkpoint immunotherapy in Pancreatic Cancer
FAK-inhibition opens the door to checkpoint immunotherapy in Pancreatic Cancer Open
Immunotherapy has had remarkable success in the treatment of some cancer types. However, pancreatic cancer has remained largely refractory to immunotherapy, including immune checkpoint inhibitors. Recently, Jiang and colleagues identified …
View article: Imaging drug uptake by bioorthogonal stimulated Raman scattering microscopy
Imaging drug uptake by bioorthogonal stimulated Raman scattering microscopy Open
Stimulated Raman scattering (SRS) microscopy in tandem with bioorthogonal Raman labelling enables intracellular drug concentrations, distribution and therapeutic response to be measured in living cells.
View article: FAK goes nuclear to control antitumor immunity—a new target in cancer immuno-therapy
FAK goes nuclear to control antitumor immunity—a new target in cancer immuno-therapy Open
Evading the antitumor immune response is important for the survival and progression of cancer. Recently, we identified an unexpected role for nuclear Focal Adhesion Kinase (FAK) activity in the control of tumor Treg levels and immune evasi…
View article: Stimulated Raman scattering microscopy: an emerging tool for drug discovery
Stimulated Raman scattering microscopy: an emerging tool for drug discovery Open
Stimulated Raman scattering and the use of bioorthogonal tags provide novel imaging platforms to facilitate the drug discovery process.