Abstract
Background: Nimotuzumab is shown to be efficacious in advanced pancreatic cancer treatment, but its predictive marker has not been established.
Objective: To investigate the impact of EGFR and KRAS status on antitumor efficacy of nimotuzumab and to explore its underlying mechanism. Methods: EGFR expressions of pancreatic cancer cell lines, BxPC3, Panc-1, and Patu-8988, were analyzed by Western blot and immunocytochemistry, and KRAS status was determined by gene sequencing. Anti-tumor effect of nimotuzumab were evaluated in vitro and in vivo. The expressions of related molecules in EGFR pathway and IL-6 was analyzed by Western blot, immunohistochemistry, and/or real-time PCR. Results: BxPC3 cells had wild type KRAS and high-level EGFR; Panc-1 cells had mutant KRAS (G13A) and low-level EGFR; Patu-8988 cells had mutant KRAS (G12V) and high-level EGFR. Nimotuzumab did not affect cell proliferation or apoptosis in vitro. Growth of BxPC3 and Patu-8988 xenografts were significantly inhibited by nimotuzumab, but not Panc-1 xenografts, compared with that of the control group. Expression of EGFR in BxPC3 and Patu-8988 xenografts was significantly reduced by nimotuzumab. The IL-6 expression in BxPC3 and Patu-8988 xenografts was higher than that in Panc-1 xenografts in the control group, and was significantly reduced by nimotuzumab. Conclusion: Pancreatic cancer cells with EGFR high expression were more sensitive to nimotuzumab in vivo. KRAS status had no impact on anti-tumor efficacy of nimotuzumab in pancreatic cancer cells.Keywords: Pancreatic cancer, nimotuzumab, predictive marker, EGFR, KRAS mutation.
Current Cancer Drug Targets
Title:EGFR High Expression, but not KRAS Status, Predicts Sensitivity of Pancreatic Cancer Cells to Nimotuzumab Treatment In Vivo
Volume: 17 Issue: 1
Author(s): Chenfei Zhou, Liangjun Zhu, Jun Ji, Fangmi Ding, Chao Wang, Qu Cai, Yingyan Yu, Zhenggang Zhu and Jun Zhang
Affiliation:
Keywords: Pancreatic cancer, nimotuzumab, predictive marker, EGFR, KRAS mutation.
Abstract: Background: Nimotuzumab is shown to be efficacious in advanced pancreatic cancer treatment, but its predictive marker has not been established.
Objective: To investigate the impact of EGFR and KRAS status on antitumor efficacy of nimotuzumab and to explore its underlying mechanism. Methods: EGFR expressions of pancreatic cancer cell lines, BxPC3, Panc-1, and Patu-8988, were analyzed by Western blot and immunocytochemistry, and KRAS status was determined by gene sequencing. Anti-tumor effect of nimotuzumab were evaluated in vitro and in vivo. The expressions of related molecules in EGFR pathway and IL-6 was analyzed by Western blot, immunohistochemistry, and/or real-time PCR. Results: BxPC3 cells had wild type KRAS and high-level EGFR; Panc-1 cells had mutant KRAS (G13A) and low-level EGFR; Patu-8988 cells had mutant KRAS (G12V) and high-level EGFR. Nimotuzumab did not affect cell proliferation or apoptosis in vitro. Growth of BxPC3 and Patu-8988 xenografts were significantly inhibited by nimotuzumab, but not Panc-1 xenografts, compared with that of the control group. Expression of EGFR in BxPC3 and Patu-8988 xenografts was significantly reduced by nimotuzumab. The IL-6 expression in BxPC3 and Patu-8988 xenografts was higher than that in Panc-1 xenografts in the control group, and was significantly reduced by nimotuzumab. Conclusion: Pancreatic cancer cells with EGFR high expression were more sensitive to nimotuzumab in vivo. KRAS status had no impact on anti-tumor efficacy of nimotuzumab in pancreatic cancer cells.Export Options
About this article
Cite this article as:
Zhou Chenfei, Zhu Liangjun, Ji Jun, Ding Fangmi, Wang Chao, Cai Qu, Yu Yingyan, Zhu Zhenggang and Zhang Jun, EGFR High Expression, but not KRAS Status, Predicts Sensitivity of Pancreatic Cancer Cells to Nimotuzumab Treatment In Vivo, Current Cancer Drug Targets 2017; 17 (1) . https://dx.doi.org/10.2174/1568009616666161013101657
DOI https://dx.doi.org/10.2174/1568009616666161013101657 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Mining the Dark Matter of the Cancer Proteome for Novel Biomarkers
Current Cancer Therapy Reviews Cytotoxic Action of N-aryl, Furan-derived Aminophosphonates against HT29 and HCT116 Cancer Cell Lines
Anti-Cancer Agents in Medicinal Chemistry Tyrosine Kinases as Molecular Targets to Inhibit Cancer Progression and Metastasis
Current Pharmaceutical Design Anti-EGFR Therapy: Strategies in Head and Neck Squamous Cell Carcinoma
Recent Patents on Anti-Cancer Drug Discovery Green Tea Catechins as Novel Antitumor and Antiangiogenic Compounds
Current Medicinal Chemistry - Anti-Cancer Agents Recent Patents Reveal Microtubules as Persistent Promising Target for Novel Drug Development for Cancers
Recent Patents on Anti-Infective Drug Discovery MicroRNAs and Chronic Inflammation Contribution to Gastrointestinal Integrity
Current Medicinal Chemistry Clopidogrel, Aspirin and Proton Pump Inhibition after Percutaneous Valve Implants: An Update
Current Pharmaceutical Design Role of Inflammation and Tumor Microenvironment in the Development of Gastrointestinal Cancers: What Induced Pluripotent Stem Cells Can Do?
Current Stem Cell Research & Therapy Editorial [Hot Topic: Inflammation as Target for Pharmaceutical Intervention in Cancer (Executive Editors: R.M. Schiffelers and K.E. de Visser)]
Current Pharmaceutical Design Monitoring T Cell Responses to Cancer Immunotherapy: Can We Now Identify Biomarkers Predicting Patients Who will be Responders
Current Cancer Therapy Reviews DLX6-AS1: An Indispensable Cancer-related Long Non-coding RNA
Current Pharmaceutical Design Phosphorylation-Specific Prolyl Isomerase Pin1 as a new Diagnostic and Therapeutic Target for Cancer
Current Cancer Drug Targets Natural Products Targeting Cancer Stem Cells: A Revisit
Current Medicinal Chemistry Molecular and Clinical Analysis of Predictive Biomarkers in Non-Small-Cell Lung Cancer
Current Medicinal Chemistry Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole
Current Drug Metabolism Recent Clinical Trials in Non-Small Cell Lung Cancer
Current Cancer Therapy Reviews Heterocyclic Drug-polymer Conjugates for Cancer Targeted Drug Delivery
Anti-Cancer Agents in Medicinal Chemistry Structure and Expression of Different Serum Amyloid A (SAA) Variants and their Concentration-Dependent Functions During Host Insults
Current Medicinal Chemistry Head and Neck Cancer Treatments through Chemotherapy to Magnetic Systems: Perspectives and Challenges
Current Radiopharmaceuticals