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Pancreatic Neoplasms: HELP
Articles by C. David James
Based on 2 articles published since 2010
(Why 2 articles?)

Between 2010 and 2020, C. James wrote the following 2 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Article Use of a genome-wide haploid genetic screen to identify treatment predicting factors: a proof-of-principle study in pancreatic cancer. 2017

Ma, Yuk Ting / Leonard, Sarah M / Gordon, Naheema / Anderton, Jennifer / James, Claire / Huen, David / Woodman, Ciaran B / Palmer, Daniel H. ·School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom. · Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom. · Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom. ·Oncotarget · Pubmed #28969017.

ABSTRACT: The ability to develop a comprehensive panel of treatment predicting factors would significantly improve our ability to stratify patients for cytotoxic or targeted therapies, and prevent patients receiving ineffective treatments. We have investigated if a recently developed genome-wide haploid genetic screen can be used to reveal the critical mediators of response to anticancer therapy. Pancreatic cancer is known to be highly resistant to systemic therapy. Recently epigenetic changes have been shown to be a key determinant in the maintenance of subpopulations of cancer cells with high-level resistance to cytotoxic therapy. We show that in human pancreatic cancer cell lines, treatment with the potent class I histone deacetylase inhibitor, entinostat, synergistically enhances gemcitabine-induced inhibition of cell proliferation and apoptosis. Using a genome-wide haploid genetic screen, we identified deoxycytidine kinase (DCK) as one of the genes with the highest degree of insertional enrichment following treatment with gemcitabine and entinostat; DCK is already known to be the rate-limiting activating enzyme for gemcitabine. Immunoblotting confirmed loss of DCK protein expression in the resistant KBM7 cells. CRISPR/Cas-9 inactivation of DCK in pancreatic cancer cell lines resulted in resistance to gemcitabine alone and in combination with entinostat. We have identified gemcitabine and entinostat as a potential new combination therapy in pancreatic cancer, and in this proof-of-principle study we have demonstrated that a recently developed haploid genetic screen can be used as a novel approach to identify the critical genes that determine treatment response.

2 Article Identification and analysis of in vivo VEGF downstream markers link VEGF pathway activity with efficacy of anti-VEGF therapies. 2013

Brauer, Matthew J / Zhuang, Guanglei / Schmidt, Maike / Yao, Jenny / Wu, Xiumin / Kaminker, Joshua S / Jurinka, Stefanie S / Kolumam, Ganesh / Chung, Alicia S / Jubb, Adrian / Modrusan, Zora / Ozawa, Tomoko / James, C David / Phillips, Heidi / Haley, Benjamin / Tam, Rachel N W / Clermont, Anne C / Cheng, Jason H / Yang, Sherry X / Swain, Sandra M / Chen, Daniel / Scherer, Stefan J / Koeppen, Hartmut / Yeh, Ru-Fang / Yue, Peng / Stephan, Jean-Philippe / Hegde, Priti / Ferrara, Napoleone / Singh, Mallika / Bais, Carlos. ·Genentech, Inc., 1 DNA Way, South San Francisco, CA 94131, USA. ·Clin Cancer Res · Pubmed #23685835.

ABSTRACT: PURPOSE: The aim of this study was to identify conserved pharmacodynamic and potential predictive biomarkers of response to anti-VEGF therapy using gene expression profiling in preclinical tumor models and in patients. EXPERIMENTAL DESIGN: Surrogate markers of VEGF inhibition [VEGF-dependent genes or VEGF-dependent vasculature (VDV)] were identified by profiling gene expression changes induced in response to VEGF blockade in preclinical tumor models and in human biopsies from patients treated with anti-VEGF monoclonal antibodies. The potential value of VDV genes as candidate predictive biomarkers was tested by correlating high or low VDV gene expression levels in pretreatment clinical samples with the subsequent clinical efficacy of bevacizumab (anti-VEGF)-containing therapy. RESULTS: We show that VDV genes, including direct and more distal VEGF downstream endothelial targets, enable detection of VEGF signaling inhibition in mouse tumor models and human tumor biopsies. Retrospective analyses of clinical trial data indicate that patients with higher VDV expression in pretreatment tumor samples exhibited improved clinical outcome when treated with bevacizumab-containing therapies. CONCLUSIONS: In this work, we identified surrogate markers (VDV genes) for in vivo VEGF signaling in tumors and showed clinical data supporting a correlation between pretreatment VEGF bioactivity and the subsequent efficacy of anti-VEGF therapy. We propose that VDV genes are candidate biomarkers with the potential to aid the selection of novel indications as well as patients likely to respond to anti-VEGF therapy. The data presented here define a diagnostic biomarker hypothesis based on translational research that warrants further evaluation in additional retrospective and prospective trials.