ArticleClinical cancer research : an official journal of the American Association for Cancer Research2008
Proteasome inhibition activates epidermal growth factor receptor (EGFR) and EGFR-independent mitogenic kinase signaling pathways in pancreatic cancer cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The trial behind it
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Who cites it
33 citing papers in PubMed, 69 citations in OpenAlex.
- Trial
- A multicenter, phase II study of bortezomib (PS-341) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma.Investigational new drugs · 2011Trial
- Marizomib in the therapy of brain tumors-how far did we go and where do we stand?Pharmacological reports : PR · 2025Review
- Targeting the ubiquitin-proteasome system in a pancreatic cancer subtype with hyperactive MYC.Molecular oncology · 2020Article
- Recent insights how combined inhibition of immuno/proteasome subunits enables therapeutic efficacy.Genes and immunity · 2020Review
- Marizomib suppresses triple-negative breast cancer via proteasome and oxidative phosphorylation inhibition.Theranostics · 2020Article
- A phase I study of HER1, HER2 dual kinase inhibitor lapatinib plus the proteasome inhibitor bortezomib in patients with advanced malignancies.Cancer chemotherapy and pharmacology · 2019Article
- Review
- Marizomib activity as a single agent in malignant gliomas: ability to cross the blood-brain barrier.Neuro-oncology · 2016Article
- ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2.The Biochemical journal · 2016Article
- Role of glycosyltransferase PomGnT1 in glioblastoma progression.Neuro-oncology · 2015Article
- Chemoprevention of lung tumorigenesis by intranasally administered diindolylmethane in A/J mice.Carcinogenesis · 2013Article
- The 26S proteasome complex: an attractive target for cancer therapy.Biochimica et biophysica acta · 2012Review
- Early tumor progression associated with enhanced EGFR signaling with bortezomib, cetuximab, and radiotherapy for head and neck cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2011Article
- Proteasome inhibitors in cancer therapy.Journal of cell communication and signaling · 2011Article
- Proteasome inhibitor MG-132 induces C6 glioma cell apoptosis via oxidative stress.Acta pharmacologica Sinica · 2011Article
- Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials.Current cancer drug targets · 2011Review
- p21(WAF1/CIP1) upregulation through the stress granule-associated protein CUGBP1 confers resistance to bortezomib-mediated apoptosis.PloS one · 2011Article
- Salinosporamide natural products: Potent 20 S proteasome inhibitors as promising cancer chemotherapeutics.Angewandte Chemie (International ed. in English) · 2010Review
- Novel therapies for pancreatic cancer: setbacks and progress.Future oncology (London, England) · 2010Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
purposeIn the current study, we investigate the activation of antiapoptotic signaling pathways in response to proteasome inhibitor treatment in pancreatic cancer and evaluate the use of concomitant inhibition of these pathways to augment proteasome inhibitor treatment responses. EXPERIMENTAL
designPancreatic cancer cell lines and mouse flank xenografts were treated with proteasome inhibitor alone or in combination with chemotherapeutic compounds (gemcitabine, erlotinib, and bevacizumab), induction of apoptosis and effects on tumor growth were assessed. The effect of bortezomib (a first-generation proteasome inhibitor) and NPI-0052 (a second-generation proteasome inhibitor) treatment on key pancreatic mitogenic and antiapoptotic pathways [epidermal growth factor receptor, extracellular signal-regulated kinase, and phosphoinositide-3-kinase (PI3K)/AKT] was determined and the ability of inhibitors of these pathways to enhance the effects of proteasome inhibition was assessed in vitro and in vivo.
resultsOur data showed that proteasome inhibitor treatment activates antiapoptotic and mitogenic signaling pathways (epidermal growth factor receptor, extracellular signal-regulated kinase, c-Jun-NH2-kinase, and PI3K/AKT) in pancreatic cancer. Additionally, we found that activation of these pathways impairs tumor response to proteasome inhibitor treatment and inhibition of the c-Jun-NH2-kinase and PI3K/AKT pathways increases the antitumor effects of proteasome inhibitor treatment.
conclusionThese preclinical studies suggest that targeting proteasome inhibitor-induced antiapoptotic signaling pathways in combination with proteasome inhibition may augment treatment response in highly resistant solid organ malignancies. Further evaluation of these novel treatment combinations in clinical trials is warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.