Targeting inflammation and immune response in HNSCC therapy

项目概要 对表皮生长因子受体（EGFR）抑制剂西妥昔单抗的总体反应较差且耐药， 无论是内在的还是后天的，都是一个关键问题。因此，阐明贫困发生机制势在必行。 对西妥昔单抗的反应并制定增强肿瘤对西妥昔单抗的反应并改善患者的策略 结果。我的总体研究兴趣集中在炎症和免疫反应上 HNSCC 患者肿瘤进展的机制和肿瘤对西妥昔单抗的不良反应。我的论文 研究重点是 IL-1 通路在 HNSCC 西妥昔单抗肿瘤反应中的重要作用 我的论文研究的总体假设是 IL-1 阻断将提高抗- 西妥昔单抗在 HNSCC 中的肿瘤疗效。迄今为止我的论文研究项目的结果非常有力 支持这一假设，表明使用中和性 IL-1 α (IL-1α) 抗体对 IL-1 的阻断作用增加 在异种移植小鼠模型中，HNSCC 肿瘤对西妥昔单抗的反应，IL-1α 可能是一个重要的因素 预测 HNSCC 患者对西妥昔单抗的肿瘤反应的生物标志物。对于我论文的其余部分 研究项目中，我将继续使用 FDA 批准的 IL-1 受体拮抗剂（IL- 1RA) 在 HNSCC 小鼠模型中阿那白滞素联合西妥昔单抗，并评估其潜在机制 肿瘤对联合药物治疗的反应。最后，在博士后期间我感兴趣的是 抗IL-1疗法与抗CTLA4/PD1疗法联合治疗HNSCC是目前癌症治疗的趋势 包括 HNSCC 的目的是使用抗 CTLA4/PD1 疗法激活免疫系统。总的来说，我相信这 F99/K00 奖将帮助我建立专注于炎症和免疫的研究生涯 反应作为肿瘤对药物治疗反应的重要参与者，并为我成为一名 成功的独立调查员。

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.