PREOPERATIVE TREATMENT OF LUNG CANCER WITH rhuMab VEGF

描述(申请人提供)：系统性治疗慢性阻塞性肺疾病 在过去的25年里取得了进步。这鼓励了调查人员 评价早期肺癌患者术前化疗的效果 疾病。在同一时间框架内，对 导致肺癌进展的分子事件导致了新的 旨在干扰关键生长调节的治疗策略 小路。紧张的临床和科学研究的一个领域是 侵袭性肿瘤招募新血管生长的能力。一个重要的 血管生成的途径是通过血管内皮生长因子 (血管内皮生长因子)，它向血管内皮细胞发送有丝分裂信号。许多 肿瘤通过自主产生血管内皮生长因子来劫持这一途径。的发展。 干扰血管内皮生长因子途径的药物试剂一直是一个主要的 调查人员的目标。其中一个试剂是rhuMAb VEGF，一种重组的， 人源化抗血管内皮生长因子的单抗。临床前和临床早期 研究支持了rhuMAb VEGF可能是一种活性的假说。 抗癌剂(特别是与 化疗药物)。我们假设早期的治疗是用 化疗与抗血管生成策略相结合将显示增强 疗效和在理解分子基础方面的回报 肿瘤对这些药物的反应将是巨大的。我们有三个具体目标 这项提议。1)术前大黄单抗联合血管内皮细胞生长因子的临床研究 可切除的非小细胞肺癌化疗后手术切除。2)分析 肿瘤血管生成的组织学和分子标志物(包括血管内皮生长因子、血管内皮生长因子 受体、细胞凋亡和肿瘤血管密度)。3) 组织学和分子标志物与临床反应和临床反应的比较 研究前/治疗后的放射成像(CT和PET扫描)。小心 本研究收集的临床和生物学信息的比较/分析 可能也会增强我们对肿瘤生长和进展的了解 作为对治疗的反应。

DESCRIPTION (provided by applicant): Systemic treatment of patients with improvements over the last 25 years. This has encouraged investigators to evaluate the benefit of preoperative chemotherapy in patients with early stage disease. Over the same time frame, improvements in the understanding of the molecular events that lead to the progression of lung cancer have led to novel therapeutic strategies designed to interfere with critical growth regulatory pathways. One area of intense clinical and scientific investigation has been the ability of invasive tumors to recruit new blood vessel growth. An important pathway of angiogenesis is through the vascular endothelial growth factor (VEGF) which sends a mitogenic signal to vascular endothelial cells. Many tumors hijack this pathway by autonomously producing VEGF. The development of pharmaceutical reagents to interfere with the VEGF pathway has been a major goal of investigators. One such reagent is rhuMAb VEGF, a recombinant, humanized monoclonal antibody to VEGF. Preclinical and early clinical investigations have supported the hypothesis that rhuMAb VEGF may be an active anti-cancer agent (particularly when administered in combination with chemotherapeutic agents). We hypothesize that earlier treatment with chemotherapy combined with anti-angiogenic strategies will show enhanced efficacy and that the payoff in terms of understanding the molecular basis of tumor response to these agents will be great. We have three specific aims in this proposal. 1) A clinical study of preoperative rhuMAb VEGF plus chemotherapy for resectable NSCLC followed by surgical resection. 2) Analysis of histologic and molecular markers of tumor angiogenesis (including VEGF, VEGF receptors, apoptosis and tumor blood vessel density) in resection specimens. 3) Comparison of histologic and molecular markers with clinical response and pre-study/post-treatment radiographic imaging (CT and PET scanning). Careful comparison/analysis of clinical and biologic information gathered in this study will likely enhance our understanding of tumor growth and progression as well as response to therapy.