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Targeting inflammation and immune response in HNSCC therapy

HNSCC 治疗中针对炎症和免疫反应

基本信息

批准号：
9438266
负责人：
Madelyn Espinosa-Cotton
金额：
$ 3.1万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-14 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9438266
关键词：
Antibodies Area Award Biological Markers CTLA4 gene Cancer Immunology Science Cell Survival Cell physiology Cells Cetuximab Combination Drug Therapy Data Data Set Doctor of Philosophy Epidermal Growth Factor Receptor Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor FDA approved Flow Cytometry Gene Expression Genes Genetic Goals Head and Neck Squamous Cell Carcinoma Human Immune Immune response Immune system Immunocompetent In Vitro Inflammation Inflammatory Innate Immune Response Interleukin-1 Interleukin-1 Receptors Interleukin-1 alpha Interleukin-6 Interleukin-8 Knowledge Link Malignant Epithelial Cell Modality Neoplasm Metastasis Oxidation-Reduction Pathway interactions Patient-Focused Outcomes Patients Pharmacotherapy Play Production Reactive Oxygen Species Recombinants Recruitment Activity Research Research Personnel Research Project Grants Resistance Rheumatoid Arthritis Role Schools Serum Signal Transduction T-Lymphocyte Testing The Cancer Genome Atlas Translating Tumor Promotion Work Xenograft procedure adaptive immune response anakinra angiogenesis cancer cachexia cancer therapy career cell growth cytokine effective therapy improved interest knock-down mouse model neoplastic cell novel therapeutics outcome forecast overexpression pre-clinical response skills trend tumor tumor growth tumor microenvironment tumor progression

项目摘要

Project Summary Overall response to the epidermal growth factor receptor (EGFR) inhibitor cetuximab is poor and resistance, both intrinsic and acquired, is a critical issue. Therefore it is imperative to elucidate the mechanisms of poor response to cetuximab and develop strategies to enhance tumor response to cetuximab and improve patient outcomes. My overall research interests center around inflammation and immune response as key mechanisms of tumor progression in HNSCC patients and poor tumor response to cetuximab. My dissertation research focuses on the IL-1 pathway as an important player in tumor response to cetuximab in HNSCC patients and the overall hypothesis of my dissertation research is that IL-1 blockade will improve the anti- tumor efficacy of cetuximab in HNSCC. Findings from my dissertation research project thus far strongly support this hypothesis indicating that IL-1 blockade using a neutralizing IL-1 alpha (IL-1α) antibody increased HNSCC tumor response to cetuximab in xenograft mouse models and that IL-1α may be an important biomarker to predict tumor response to cetuximab for HNSCC patients. For the remainder of my dissertation research project, I will continue to test my hypothesis using the FDA approved IL-1 receptor antagonist (IL- 1RA) anakinra in combination with cetuximab in HNSCC mouse models, and assess potential mechanisms of tumor response to combination drug therapy. Finally, during my postdoctoral period I am interested in combining anti-IL-1 therapy with anti-CTLA4/PD1 therapy for HNSCC since the current trend in cancer therapy including HNSCC is to activate the immune system using anti-CTLA4/PD1 therapies. Overall, I believe that this F99/K00 award will assist me in establishing my research career focused on inflammation and immune response as important players in tumor response to drug therapy and pave the way for me to become a successful independent investigator.

项目总结