MULTI-TARGETED RNAI THERAPEUTICS FOR TREATMENT OF LUNG CANCER (NSCLC)

用于治疗肺癌 (NSCLC) 的多靶点 RNAI 疗法

• 批准号: 7670638
• 负责人: Patrick Y Lu
• 金额: $ 25万
• 依托单位: SIRNAOMICS, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7670638
• 关键词: A549; Animal Model; Apoptosis; Avastin; Breast; Cancer Etiology; Cancer Patient; Carboplatin; Cell Culture Techniques; Cells; Cessation of life; Cleaved cell; Colon; Colorectal; Computer Simulation; Disease; Down-Regulation; Drug Formulations; EGFR Protein Overexpression; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Erlotinib; Gefitinib; Gene Expression; Gene Silencing; Gene Targeting; Generations; Genes; Grant; Histidine; In Vitro; Innovative Therapy; Ligands; Lipids; Lysine; Malignant Epithelial Cell; Malignant Neoplasms; Malignant neoplasm of lung; Mediating; Mediator of activation protein; Messenger RNA; Modality; Modeling; Molecular; Molecular Target; Monoclonal Antibodies; Mus; Mutation; Non-Small-Cell Lung Carcinoma; Oncogenic; Paclitaxel; Pathogenesis; Pathology; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Placebos; Platelet-Derived Growth Factor; Polymers; Prostate; Protein Tyrosine Kinase; Protocols documentation; RNA Interference; RNA-Induced Silencing Complex; Resistance; Reverse Transcriptase Polymerase Chain Reaction; Safety; Series; Small Interfering RNA; Staging; Survival Rate; System; Tail; Technology; Testing; Therapeutic; Therapeutic Agents; Toxic effect; Treatment Protocols; United States; United States Food and Drug Administration; Vascular Endothelial Growth Factors; Veins; Xenograft procedure; angiogenesis; base; bevacizumab; celecoxib; chemotherapy; drug candidate; drug testing; fighting; improved; in vivo; inhibitor/antagonist; molecular oncology; nanoparticle; novel; novel therapeutic intervention; novel therapeutics; preclinical study; public health relevance; response; small molecule; statistics; therapeutic target; tumor; tumor growth; tumor xenograft; weapons

DESCRIPTION (provided by applicant): Lung cancer is the leading cause of cancer-related death in the United States and is responsible for over 160,000 patient deaths from their lung cancer this year, more than that of breast, colorectal, prostate, colon and other cancers combined. With the existing therapeutic efforts, patients with lung cancer have a 5-year survival rate of less than 15%. There is a tremendous unmet need for treatment of Non-Small-Cell lung cancer, represent 85% of all lung cancer patients. Efforts have recently been directed toward developing novel therapies based on a growing understanding of molecular oncology. Understanding the molecular mechanisms involved in the pathogenesis of lung cancer can provide opportunities to develop innovative therapies for NSCLC. In this proposal, we proposed a novel multi-targeted siRNA therapeutic for NSCLC treatment. We will test this drug candidate in A549 and H460 xenograft tumor models for its antitumor efficacy and safety profiles. We will also use HKP and PTL nanoparticle to further enhance the this siRNA cocktail therapeutics, targeting EGFR, VEGF, Cox-2 or PDGF oncogenic genes. Furthermore, we test this drug in combination with current targeted therapeutics of small molecules and monoclonal antibodies, such as Tarceva, Iressa and Avastin, in the animal models, for an alternative therapeutics to treat NSCLC. PUBLIC HEALTH RELEVANCE: Lung cancer is the leading cause of cancer-related death in the United States and is responsible for over 160,000 patient deaths from their lung cancer this year, more than that of breast, colorectal, prostate, colon and other cancers combined. There is a tremendous unmet need for treatment of Non-Small-Cell lung cancer, represent 85% of all lung cancer patients. In this proposal, we use a novel RNAi technology approach to develop a multi-targeted siRNA therapeutics for NSCLC treatment. The HKP and PTL nanoparticle technologies will greatly enhance systemic delivery of this siRNA cocktail therapeutics, targeting EGFR, VEGF, Cox-2 or PDGF oncogenic genes. Combining this siRNA drug with current targeted therapeutics of small molecule and monoclonal antibodies will provide us a powerful weapon to fight this deadly disease, NSCLC.

描述（由申请人提供）：肺癌是美国癌症相关死亡的主要原因，今年有超过160，000名患者死于肺癌，超过乳腺癌、结肠直肠癌、前列腺癌、结肠癌和其他癌症的总和。在现有的治疗努力下，肺癌患者的5年生存率低于15%。非小细胞肺癌的治疗需求巨大，占所有肺癌患者的85%。最近的努力已经指向开发新的疗法的基础上不断增长的理解分子肿瘤学。了解肺癌发病机制的分子机制可以为开发NSCLC的创新疗法提供机会。在这个提案中，我们提出了一种新的多靶点siRNA治疗NSCLC的治疗。我们将在A549和H460异种移植肿瘤模型中测试该候选药物的抗肿瘤疗效和安全性。我们还将使用HKP和PTL纳米颗粒来进一步增强这种siRNA鸡尾酒疗法，靶向EGFR、VEGF、考克斯-2或PDGF致癌基因。此外，我们在动物模型中测试了这种药物与目前小分子和单克隆抗体的靶向治疗剂（如特罗凯、易瑞沙和阿瓦斯丁）的组合，以寻找治疗NSCLC的替代疗法。公共卫生关系：肺癌是美国癌症相关死亡的主要原因，今年有超过16万名患者死于肺癌，超过乳腺癌、结直肠癌、前列腺癌、结肠癌和其他癌症的总和。非小细胞肺癌的治疗需求巨大，占所有肺癌患者的85%。在这个提议中，我们使用一种新的RNAi技术方法来开发用于NSCLC治疗的多靶点siRNA疗法。HKP和PTL纳米颗粒技术将极大地增强靶向EGFR、VEGF、考克斯-2或PDGF致癌基因的这种siRNA鸡尾酒疗法的全身递送。将这种siRNA药物与目前的小分子和单克隆抗体靶向治疗方法相结合，将为我们提供一种强大的武器来对抗这种致命的疾病，NSCLC。