A Creative Integration of Omega-3 Fatty Acids into Pancreatic Cancer Chemotherapy

将 Omega-3 脂肪酸创造性地整合到胰腺癌化疗中

• 批准号: 8824063
• 负责人: ZHENGRONG CUI
• 金额: $ 16.86万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8824063
• 关键词: Abraxane; Acute; Address; Adverse event; Affect; Albumin-Stabilized Nanoparticle Paclitaxel; Albumins; Angiogenesis Inhibitors; Animal Model; Antineoplastic Agents; Binding; Biodistribution; Biology; Cachexia; Cancer Biology; Cancer Diagnostics; Cancer Etiology; Cancer Model; Cancer Patient; Cancer cell line; Cessation of life; Chemistry; Chemotherapy-Oncologic Procedure; Clinical; Clinical Trials; DHA-Paclitaxel; Data; Deamination; Desire for food; Desmoplastic; Development; Docosahexaenoic Acids; Dose; Drug Kinetics; Emulsions; Evaluation; Excision; Excretory function; Fatty Acids; Fish Oils; Foundations; Future; Generations; Goals; Government; Human; Infusion procedures; Intravenous; Investigational New Drug Application; Investigational Therapies; KRAS2 gene; Lead; Legal patent; Malignant Neoplasms; Malignant neoplasm of pancreas; Maximum Tolerated Dose; Metabolism; Methods; Mission; Mus; Nature; Nude Mice; Nutritional; Omega-3 Fatty Acids; Operative Surgical Procedures; Outcome; Paclitaxel; Palliative Care; Pancreatic Ductal Adenocarcinoma; Patients; Persons; Pharmacologic Substance; Prevention; Property; Public Health; Quality of life; Relative (related person); Reporting; Research; Rodent Model; Safety; Scientist; Series; Solid Neoplasm; Structure; Survival Rate; Symptoms; Testing; Time; Total Parenteral Nutrition; Toxic effect; Toxicity Tests; Transgenic Mice; Translations; Weight; Work; cancer therapy; chemotherapy; cytotoxic; cytotoxicity; effective therapy; experience; gemcitabine; gemzar; human disease; improved; innovation; mortality; mouse model; neoplastic cell; novel; novel strategies; pancreatic cancer cells; pancreatic neoplasm; preclinical efficacy; preclinical evaluation; preclinical safety; public health relevance; safety testing; standard of care; tumor; tumor growth

DESCRIPTION (provided by applicant): Pancreatic cancer is the fourth leading cause of cancer death in the U.S., with a 5-year survival rate of only 4-5%. Although significant progress has been made in the past several decades to reduce the overall mortality rate of cancer, an effective treatment for pancreatic cancer remains elusive. Only ~10% of pancreatic cancer patients are suitable for surgical resection, and the remainder is offered palliative treatment to simply extend or improve their quality of life. Approximately 85% of all pancreatic cancer patients suffer from cachexia, a devastating symptom symbolized by the loss of appetite, weight, and quality of life. The standard of care of advanced pancreatic cancer patients has been the single agent chemotherapy with gemcitabine (i.e., Gemzar(R)), which offers a survival advantage of 2-3 months compared to no treatment, and only < 25% of pancreatic cancer patients are responders to it. Our long-term goal is to improve the clinical outcomes of pancreatic cancer therapy. The current proposal combines the expertise of a pharmaceutical scientist experienced in cancer experimental therapy, a cancer biologist with expertise in pancreatic cancer biology and models, and a nutritional scientist with expertise in the chemistry and biology of omega-3 polyunsaturated fatty acids (PUFAs). Data from many clinical trials showed that fish oil rich in omega-3 PUFAs is beneficial in alleviating pancreatic cancer-related cachexia. However, there is no clear clinical evidence supporting the antitumor activity omega-3 PUFAs against pancreatic ductal adenocarcinoma. Our recent promising preliminary data demonstrated that a unique integration of omega-3 PUFAs into gemcitabine therapy significantly improves the antitumor activity of gemcitabine in mouse models of pancreatic cancer. The overall objective of the present application is to comprehensively test the safety and efficacy of this unique integration in mouse models. The primary innovative aspect of this application is the novel method of utilizing omega-3 fatty acids in improving the efficacy of gemcitabine in pancreatic cancer therapy. The proposed research is significant because it addresses the urgent need to improve the overall survival and the quality of life of pancreatic cancer patients (e.g., alleviation of cachexia). Study findings will provide the initial underpinnings for future translation of this innovation into clinical trials, with the ultimate goal of establishing a highl effective approach to pancreatic cancer chemotherapy.

描述（由申请人提供）：胰腺癌是美国癌症死亡的第四大原因，5年生存率只有4- 5%。尽管在过去几十年中在降低癌症的总体死亡率方面取得了重大进展，但胰腺癌的有效治疗仍然难以捉摸。只有约10%的胰腺癌患者适合手术切除，其余的患者仅提供姑息治疗以延长或改善其生活质量。大约85%的胰腺癌患者患有恶病质，这是一种毁灭性的症状，表现为食欲不振，体重下降和生活质量下降。晚期胰腺癌患者的护理标准是使用吉西他滨的单药化疗（即，Gemzar（R）），与不治疗相比，它提供了2-3个月的生存优势，只有< 25%的胰腺癌患者对它有反应。我们的长期目标是改善胰腺癌治疗的临床结果。目前的提案结合了一位在癌症实验治疗方面经验丰富的制药科学家，一位在胰腺癌生物学和模型方面具有专业知识的癌症生物学家，以及一位在omega-3多不饱和脂肪酸（PUFA）的化学和生物学方面具有专业知识的营养科学家的专业知识。来自许多临床试验的数据表明，富含omega-3 PUFA的鱼油有助于缓解胰腺癌相关的恶病质。然而，没有明确的临床证据支持omega-3 PUFA对胰腺导管腺癌的抗肿瘤活性。我们最近有希望的初步数据表明，将omega-3 PUFA独特地整合到吉西他滨治疗中显著提高了吉西他滨在胰腺癌小鼠模型中的抗肿瘤活性。本申请的总体目标是全面测试这种独特整合在小鼠模型中的安全性和有效性。本申请的主要创新方面是利用ω-3脂肪酸改善吉西他滨在胰腺癌治疗中的功效的新方法。这项拟议的研究意义重大，因为它解决了改善胰腺癌患者总体生存率和生活质量的迫切需要（例如，恶病质的缓解）。研究结果将为未来将这一创新转化为临床试验提供初步基础，最终目标是建立一种高效的胰腺癌化疗方法。