ArticleClinical cancer research : an official journal of the American Association for Cancer Research2008
The combination of epidermal growth factor receptor inhibitors with gemcitabine and radiation in pancreatic cancer.
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 78 papers.
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Who cites it
78 citing papers in PubMed, 121 citations in OpenAlex.
- Trial
- Prospective study of cetuximab and gemcitabine in combination with radiation therapy: feasibility and efficacy in locally advanced pancreatic head cancer.Radiation oncology (London, England) · 2015Trial
- Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2012Trial
- Trial
- Biological evaluation of novel gemcitabine analog in patient-derived xenograft models of pancreatic cancer.BMC cancer · 2023Article
- Brachytherapy via a depot of biopolymer-boundNature biomedical engineering · 2022Article
- Establishing and validating an ADCP-related prognostic signature in pancreatic ductal adenocarcinoma.Aging · 2022Article
- Calcium channel blockers potentiate gemcitabine chemotherapy in pancreatic cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Chlorogenic Acid, the Main Antioxidant in Coffee, Reduces Radiation-Induced Apoptosis and DNA Damage via NF-E2-Related Factor 2 (Nrf2) Activation in Hepatocellular Carcinoma.Oxidative medicine and cellular longevity · 2022Article
- Combinatorial Efficacy of Olaparib with Radiation and ATR Inhibitor Requires PARP1 Protein in Homologous Recombination-Proficient Pancreatic Cancer.Molecular cancer therapeutics · 2021Article
- Enhancing efficacy of gemcitabine in pancreatic patient-derived xenograft mouse models.International journal of pharmaceutics: X · 2020Article
- Expression of the Androgen Receptor Governs Radiation Resistance in a Subset of Glioblastomas Vulnerable to Antiandrogen Therapy.Molecular cancer therapeutics · 2020Article
- Increased expression of plakoglobin is associated with upregulated MAPK and PI3K/AKT signalling pathways in early resectable pancreatic ductal adenocarcinoma.Oncology letters · 2020Article
- Targeted Dual Intervention-Oriented Drug-Encapsulated (DIODE) Nanoformulations for Improved Treatment of Pancreatic Cancer.Cancers · 2020Article
- Tissue of origin dictates GOT1 dependence and confers synthetic lethality to radiotherapy.Cancer & metabolism · 2020Article
- Discovery of Icotinib-1,2,3-Triazole Derivatives as IDO1 Inhibitors.Frontiers in pharmacology · 2020Article
- Biodistribution, pharmacokinetics and radioimmunotherapy ofInvestigational new drugs · 2019Article
- Pancreatic ductal adenocarcinoma: biological hallmarks, current status, and future perspectives of combined modality treatment approaches.Radiation oncology (London, England) · 2019Review
- Mesothelin and TGF-α predict pancreatic cancer cell sensitivity to EGFR inhibitors and effective combination treatment with trametinib.PloS one · 2019Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
purposeGemcitabine-radiotherapy is a standard treatment for locally advanced pancreatic cancer. Clinical data have shown that gemcitabine plus erlotinib is superior to gemcitabine alone for advanced pancreatic cancer. Therefore, we investigated the effects of the combination of epidermal growth factor receptor inhibitors with gemcitabine and radiation on a pancreatic cancer model. EXPERIMENTAL
designEGFR signaling was analyzed by measuring phosphorylated EGFR (pEGFR(Y845, (Y1173)) and AKT (pAKT(S473)) protein levels in pancreatic cancer cell lines and tumors. The effects of scheduling on gemcitabine-mediated cytotoxicity and radiosensitization combined with erlotinib were determined by clonogenic survival. In vivo, the effects of cetuximab or erlotinib in combination with gemcitabine-radiation on the growth of BxPC-3 tumor xenografts were measured.
resultsWe found in vitro that gemcitabine induced phosphorylation of EGFR at Y845 and Y1173 that was blocked by erlotinib. Treatment of BxPC-3 cells with gemcitabine before erlotinib enhanced gemcitabine-mediated cytotoxicity without abrogating radiosensitization. In vivo, cetuximab or erlotinib in combination with gemcitabine-radiation inhibited growth compared with gemcitabine-radiation (time to tumor doubling: gemcitabine + radiation, 19 +/- 3 days; cetuximab + gemcitabine + radiation, 30 +/- 3 days; P < 0.05, erlotinib + gemcitabine + radiation 28 +/- 3 days; P < 0.1). Cetuximab or erlotinib in combination with gemcitabine-radiation resulted in significant inhibition of pEGFR(Y1173) and pAKT(S473) early in treatment, and pEGFR(Y845), pEGFR(Y1173), and pAKT(S473) by the end of treatment. This study shows a novel difference pEGFR(Y845) and pEGFR(Y1173) in response to EGFR inhibition.
conclusionsThese results show that the EGFR inhibitors cetuximab and erlotinib increase the efficacy of gemcitabine-radiation. This work supports the integration of EGFR inhibitors with gemcitabine-radiation in clinical trials for pancreatic cancer.
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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.