Concurrent Targeting of EGFR and VEGFR in Oral Squamous Cell Carcinoma

口腔鳞状细胞癌中 EGFR 和 VEGFR 的同时靶向治疗

• 批准号: 8109262
• 负责人: Seungwon Kim
• 金额: $ 10.79万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-02 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8109262
• 关键词: Affect; Area; Behavior; Biological Markers; Cancer Center; Caring; Cetuximab; Clinical Trials; Diagnosis; Disease; Down-Regulation; Endothelial Cells; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Future; Goals; Growth Factor Inhibition; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Head and neck structure; Heterogeneity; In Vitro; Malignant Epithelial Cell; Mediating; Modality; Monoclonal Antibodies; Oral cavity; Pathway interactions; Patient Selection; Patients; Physicians; Process; Production; Protein Tyrosine Kinase; Public Health; Receptor Inhibition; Recurrence; Regimen; Research Personnel; Scientist; Site; Specimen; Therapeutic; Tissues; Universities; Vascular Endothelial Growth Factor Receptor; Vascular Endothelial Growth Factors; ZD-6474; angiogenesis; base; bevacizumab; cancer therapy; career; in vivo; in vivo Model; mouth squamous cell carcinoma; neoplastic cell; novel; novel therapeutics; oncology; outcome forecast; pre-clinical; receptor; response; skills; small molecule; therapeutic target; tumor

DESCRIPTION (provided by applicant): I have previously demonstrated a commitment towards a career as physician-scientist with focus in head and neck oncology. The goal of this application is to study the antitumor mechanism of a novel therapeutic regimen in head and neck cancer. Every year, approximately 40,000 peoples will be diagnosed with squamous cell carcinomas of the head and neck area with the oral cavity being the most commonly affected site. Despite the recent advances in cancer therapy, the overall survival of patients with oral squamous cell carcinoma (OSCC) has remained unchanged in the past 30 years at approximately 50%. The prognosis is worse for those with recurrent or metastatic disease where the overall survival is approximately 6 months. Dual targeting of EGFR and VEGFR has been proposed to be a promising strategy in anticancer therapy. However, there is a tremendous heterogeneity in response of patients to EGFR and VEGFR targeted therapy. The basis for this heterogeneity has yet to be fully characterized and hinders the proper selection of patients for this therapeutic modality. The goal of this study is to comprehensively study the antitumor mechanism of dual EGFR and VEGFR targeting in OSCC. It is our hypothesis that the down-regulation of StatS in both tumor cell and endothelial compartment of OSCC mediates the enhanced antitumor effects of EGFR and VEGFR inhibition compared to the inhibition of either receptor alone. I will utilize novel in vitro and in vivo models of OSCC and angiogenesis to study his hypothesis. The preclinical findings will then be verified by analysis of tumor specimens from clinical trial of EGFR/VEGFR inhibition in patients with OSCC. The impact of this study on public health lies in establishing the basis for identification of important biomarkers of tumor behavior and therapeutic avenues in the treatment of Q.SCC. The process of performing this study will provide me with the necessary skill, coursework, and guidance towards becoming successful, independent investigator as well as furthering the care and treatment of patients with OSCC.

描述（由申请人提供）：我之前曾表现出对作为医师科学家职业的承诺，重点关注头颈肿瘤学。本申请的目的是研究头颈癌新型治疗方案的抗肿瘤机制。每年，大约有 40,000 人被诊断出患有头颈部鳞状细胞癌，其中口腔是最常见的受影响部位。尽管癌症治疗最近取得了进展，但口腔鳞状细胞癌 (OSCC) 患者的总生存率在过去 30 年中一直保持在约 50% 左右。对于复发或转移性疾病的患者，其总生存期约为 6 个月，预后较差。 EGFR 和 VEGFR 的双重靶向已被认为是抗癌治疗中一种有前途的策略。然而，患者对 EGFR 和 VEGFR 靶向治疗的反应存在巨大的异质性。这种异质性的基础尚未得到充分表征，并且阻碍了对这种治疗方式的患者的正确选择。本研究的目的是全面研究EGFR和VEGFR双重靶向治疗OSCC的抗肿瘤机制。我们的假设是，与单独抑制任一受体相比，OSCC 的肿瘤细胞和内皮室中 StatS 的下调介导了 EGFR 和 VEGFR 抑制增强的抗肿瘤作用。我将利用 OSCC 和血管生成的新型体外和体内模型来研究他的假设。然后，将通过对 OSCC 患者 EGFR/VEGFR 抑制临床试验的肿瘤标本进行分析来验证临床前研究结果。这项研究对公众健康的影响在于为鉴定肿瘤行为的重要生物标志物和治疗 Q.SCC 的治疗途径奠定了基础。进行这项研究的过程将为我提供必要的技能、课程和指导，帮助我成为成功的独立研究者，并进一步促进 OSCC 患者的护理和治疗。