In this special interview series, we profile members of The FEBS Journal editorial board to highlight their research focus, perspectives on the journal and future directions in their field. Professor Daniel Longley is the Director of the Patrick G Johnston Centre for Cancer Research at the School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, UK. He has served as an Editorial Board Member of The FEBS Journal since 2021.
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Ribosome Quality Control mitigates the cytotoxicity of ribosome collisions induced by 5-Fluorouracil.
Nucleic Acids Res
November 2024
Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast BT7 9AE, UK.
Ribosome quality control (RQC) resolves collided ribosomes, thus preventing their cytotoxic effects. The chemotherapeutic agent 5-Fluorouracil (5FU) is best known for its misincorporation into DNA and inhibition of thymidylate synthase. However, while a major determinant of 5FU's anticancer activity is its misincorporation into RNAs, the mechanisms by which cancer cells overcome the RNA-dependent 5FU toxicity remain ill-defined.
View Article and Find Full Text PDFSpatial effects of infiltrating T cells on neighbouring cancer cells and prognosis in stage III CRC patients.
J Pathol
October 2024
Department of Physiology and Medical Physics, RCSI Centre for Systems Medicine, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, Dublin, Ireland.
Colorectal cancer (CRC) is one of the most frequently occurring cancers, but prognostic biomarkers identifying patients at risk of recurrence are still lacking. In this study, we aimed to investigate in more detail the spatial relationship between intratumoural T cells, cancer cells, and cancer cell hallmarks as prognostic biomarkers in stage III colorectal cancer patients. We conducted multiplexed imaging of 56 protein markers at single-cell resolution on resected fixed tissue from stage III CRC patients who received adjuvant 5-fluorouracil (5FU)-based chemotherapy.
View Article and Find Full Text PDFUSP7 inhibitors suppress tumour neoangiogenesis and promote synergy with immune checkpoint inhibitors by downregulating fibroblast VEGF.
Clin Transl Med
April 2024
Almac Discovery Ltd., Health Science Building, Belfast, UK.
Background: Understanding how to modulate the microenvironment of tumors that are resistant to immune checkpoint inhibitors represents a major challenge in oncology.Here we investigate the ability of USP7 inhibitors to reprogram the tumor microenvironment (TME) by inhibiting secretion of vascular endothelial growth factor (VEGF) from fibroblasts.
Methods: To understand the role played by USP7 in the TME, we systematically evaluated the effects of potent, selective USP7 inhibitors on co-cultures comprising components of the TME, using human primary cells.
Identification of unique rectal cancer-specific subtypes.
Br J Cancer
May 2024
Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, 2, Ireland.
Article Synopsis
- The study critiques existing colorectal cancer subtyping methods, noting they fail to account for differences between colon and rectal tissues, especially in the context of chemotherapy.
- Researchers analyzed mRNA expression profiles from 2,121 cancer samples, discovering that neoadjuvant chemoradiotherapy alters subtype classifications in rectal cancer, leading to the identification of three specific subtypes (RSSs).
- These three subtypes (RSS1, RSS2, and RSS3) showed distinct disease-free survival rates and underlying biological characteristics, indicating that this new subtyping method outperforms traditional methods in assessing prognosis and potential treatment pathways for rectal cancer.
Spatial Effects of Infiltrating T cells on Neighbouring Cancer Cells and Prognosis in Stage III CRC patients.
bioRxiv
March 2024
Department of Physiology and Medical Physics, RCSI Centre for Systems Medicine, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, Dublin 2, Ireland.
Colorectal cancer (CRC) is one of the most frequently occurring cancers, but prognostic biomarkers identifying patients at risk of recurrence are still lacking. In this study, we aimed to investigate in more detail the spatial relationship between intratumoural T cells, cancer cells, and cancer cell hallmarks, as prognostic biomarkers in stage III colorectal cancer patients. We conducted multiplexed imaging of 56 protein markers at single cell resolution on resected fixed tissue from stage III CRC patients who received adjuvant 5-fluorouracil-based chemotherapy.
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