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.
Public Health Relevance Statement: 7. Project Narrative Multi-targeted RNAi Therapeutics for Treatment of Non-Small-Cell Lung Carcinoma (NSCLC) 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.
NIH Spending Category: Bioengineering; Biotechnology; Cancer; Gene Therapy; Genetics; Lung; Lung Cancer; Nanotechnology
Project Terms: A549; angiogenesis; Animal Model; Apoptosis; Avastin; base; bevacizumab; Breast; Cancer Etiology; Cancer Patient; Carboplatin; celecoxib; Cell Culture Techniques; Cells; Cessation of life; chemotherapy; Cleaved cell; Colon; Colorectal; Computer Simulation; Disease; Down-Regulation; drug candidate; Drug Formulations; drug testing; EGFR Protein Overexpression; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Erlotinib; fighting; Gefitinib; Gene Expression; Gene Silencing; Gene Targeting; Generations; Genes; Grant; Histidine; improved; In Vitro; in vivo; inhibitor/antagonist; Innovative Therapy; Ligands; Lipids; Lysine; Malignant Epithelial Cell; Malignant neoplasm of lung; Malignant Neoplasms; Mediating; Mediator of activation protein; Messenger RNA; Modality; Modeling; Molecular; molecular oncology; Molecular Target; Monoclonal Antibodies; Mus; Mutation; nanoparticle; Non-Small-Cell Lung Carcinoma; novel; novel therapeutic intervention; novel therapeutics; Oncogenic; Paclitaxel; Pathogenesis; Pathology; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Placebos; Platelet-Derived Growth Factor; Polymers; preclinical study; Prostate; Protein Tyrosine Kinase; Protocols documentation; public health relevance; Resistance; response; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; RNA-Induced Silencing Complex; Safety; Series; Small Interfering RNA; small molecule; Staging; statistics; Survival Rate; System; Tail; Technology; Testing; Therapeutic; Therapeutic Agents; therapeutic target; Toxic effect; Treatment Protocols; tumor; tumor growth; tumor xenograft; United States; United States Food and Drug Administration; Vascular Endothelial Growth Factors; Veins; weapons; Xenograft procedure
