Molecular Target for Liver Cancer Diagnosis and Therapy

描述（申请人提供）：肝癌是世界上最常见的恶性人类癌症之一。肝癌的发病率在美国呈上升趋势。大多数肝癌是长期形成的，通常伴有慢性肝病。这为根除或至少减缓肝癌的进展提供了机会。迫切的问题是确定可用于早期诊断和治疗干预的分子靶点。最新可用的适体和纳米颗粒技术为这一目的提供了独特的机会。与基因组学和蛋白质组学方法相比，适体技术可以利用完整的肿瘤细胞识别标记物，密切反映肿瘤的生理状态，具有显著的优势。我们的研究项目的总体目标是应用这项技术来选择和表征癌症特异性适配体，用于人类肝癌的早期诊断和治疗。我们之前的工作已经验证了几种癌症特异性适配体，包括小鼠肝癌。我们已经建立了可靠的分离培养人原代肝细胞和肝癌细胞的系统。我们还验证了人类肝癌的动物模型。在本课题中，我们将生成和测试人类肝癌特异性适配体，并验证其在癌症诊断和靶向治疗中的应用。该目标将通过三个具体目标来实现：目标1：鉴定和表征人类肝癌细胞特异性适配体；目标2。应用核酸适配体和纳米粒子诊断人肝癌；目标3。利用适体-纳米粒子-化疗药物复合物开发新型有效的靶向肿瘤治疗方法。我们的研究将在完整癌细胞的背景下确定肝癌的适体和生物标志物。适体与纳米粒子的结合将为癌症的早期诊断和靶向治疗提供有力的工具。我们获得的经验不仅对后续的临床试验有帮助，而且对其他实体肿瘤的生物标志物的发现也有重大影响。公共卫生相关性：我们的提案将解决使用新型适配体/纳米技术管理肝癌的两个最重要的问题：发现早期肝癌诊断的有效分子标记和肝癌治疗的分子标记的验证。

DESCRIPTION (provided by applicant): Liver cancer is among the most common and malignant human cancers in the world. The incidence of liver cancer is increasing in the United States. The majority of liver cancers are developed over long period of time, often with chronic liver disease. This offers a window of opportunity to eradicate or at least slow the progression of liver cancer. The urgent issue is to identify molecular targets that can be used for early diagnosis and therapeutic intervention. Newly available aptamer and nanoparticle technology provides a unique opportunity for this purpose. In comparison with genomic and proteomic approaches, the aptamer technology can identify markers using intact tumor cells, which will have significant advantages by closely reflecting the physiological state of cancer. The overall objective of our research program is to apply this technology to select and characterize cancer-specific aptamers for human liver cancer early diagnosis and therapy. Our previous work has validated several cancer-specific aptamers, including murine liver cancer. We have established a reliable system to isolate and culture human primary hepatocytes and liver cancer cells. We have also validated an animal model for human liver cancer. In this proposal, we will generate and test human liver cancer-specific aptamers, and validate their application in cancer diagnosis and target therapy. The goal will be achieved through three specific aims: Aim 1: To identify and characterize human liver cancer cell-specific aptamers; Aim 2. To apply aptamers and nanoparticles for human liver cancer diagnosis; Aim 3. To develop novel and effective target cancer therapy using aptamers-nanoparticle-chemotherapy agent complexes. Our investigation will identify aptamers and biomarkers for liver caner in the context of intact cancer cells. The combination of aptamer and nanoparticles will provide a powerful tool for cancer early diagnosis and targeting therapy. The experience we gain will not only be instrumental for subsequent clinical trails but also have significant impact on biomarker discovery of other solid tumors. PUBLIC HEALTH RELEVANCE: Our proposal will address two of the most important issues in liver cancer management using novel aptamer/nanotechnology: discovery of effective molecular markers for early liver cancer diagnosis and validation of molecular markers for liver cancer therapy.