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

描述（由申请人提供）：胰腺癌是美国第四大癌症死亡原因，5年生存率仅为4-5%。尽管在过去的几十年里，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，其余患者接受姑息治疗，单纯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。晚期胰腺癌患者的标准治疗一直是吉西他滨单药化疗（即Gemzar®），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（PUFAs）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。许多临床试验的数据表明，富含omega-3 PUFAs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 PUFAs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 PUFAs独特地整合到吉西他滨治疗中，可显着提高吉西他滨在胰腺癌小鼠模型中的抗肿瘤活性。本应用程序的总体目标是在小鼠模型中全面测试这种独特整合的安全性和有效性。该应用的主要创新方面是利用omega-3脂肪酸的新方法来提高吉西他滨在胰腺癌治疗中的疗效。提出的研究具有重要意义，因为它解决了提高胰腺癌患者总体生存率和生活质量的迫切需要（例如，减轻恶病质）。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。

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®), 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.