Individualized Treatment of Pancreatic Cancer

胰腺癌的个体化治疗

• 批准号: 7105931
• 负责人: MANUEL HIDALGO
• 金额: $ 29.01万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-06 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7105931
• 关键词: clinical research; model; neoplasm /cancer; pancreas neoplasms; xenotransplantation

DESCRIPTION (provided by applicant): Pancreatic cancer is a lethal disease. Empirical development of new drugs has not resulted in any meaningful improvement in survival. New strategies are urgently needed to combat this disease. We have developed and optimized a low-passage xenograft model that may permit an individualize approach to the treatment of patients with pancreatic cancer. Freshly pancreatic cancer tissues obtained at the time of surgical resection of pancreatic cancer are implanted in nude mice. Xenografted tumors can be treated with anticancer agent to determine their in vivo activity. In previous studies we have mastered this model and have a high take on rate and excellent in vivo results. We have also shown that the xenografted tumors closely resemble at the histology, gene mutation and selected gene expression data the biological features of the primary tumor from which they were generated. Sucessive passage in mice does not influence the resistant/susceptibility properties of the tumors to the drugs we have preliminarily tested and does not result in mayor changes in biological features. Because tumors can be indefinitely propagated in the mice the model is also very well suited to investigate biological markers that predict response and/or resistance to drugs. This translational application is to utilize the above mentioned preclinical model for cancer treatment. The hypothesis to be tested is that model-based selection of drugs for patient's treatment will result in better outcome than expected with conventional drugs. We propose the following three Specific Aims: 1) to determine the activity of a series of available anticancer agents against a set of xenografted tumors obtained from patients with resected pancreatic cancer; 2) to conduct a phase II clinical trial in which patients whose tumor was xenografted in the mice will be treated at the time of progression with model-selected agent and; 3) to explore biological markers of response to treatment agents in tumor tissues. We expect this approach will validate the use of the low-passage xenograft model to predict susceptibility to a drug. If correct, this model will then be invaluable to discover biomarkers predicting drug response and as a screening model to select drug for clinical development in pancreatic cancer.

描述（由申请人提供）：胰腺癌是一种致命疾病。新药的经验发展并未导致生存的任何有意义的改善。迫切需要采取新策略来打击这种疾病。我们已经开发并优化了一个低通的异种移植模型，该模型可能允许对胰腺癌患者的治疗方式进行个性化方法。在胰腺癌手术切除时获得的新胰腺癌组织植入了裸鼠。异种移植肿瘤可以用抗癌剂治疗，以确定其体内活性。在先前的研究中，我们已经掌握了该模型，并具有很高的率和出色的体内结果。我们还表明，异种移植的肿瘤在组织学，基因突变和选择基因表达数据上与产生的原发性肿瘤的生物学特征相似。小鼠中的成功通过不会影响肿瘤对我们先前测试的药物的抗性/敏感性，并且不会导致市长的生物学特征变化。由于肿瘤可以在小鼠中无限期地传播，因此模型也非常适合研究预测对药物反应和/或抗性的生物学标记。这种翻译应用是利用上述临床前模型进行癌症治疗。要测试的假设是，基于模型的患者治疗药物选择将带来比常规药物预期的更好的结果。我们提出以下三个特定目的：1）确定一系列可用的抗癌药的活性，以从切除的胰腺癌患者获得的一组异种移植肿瘤； 2）进行II期临床试验，在该试验中，将用模型选择的剂进展时治疗小鼠肿瘤的患者。 3）探索肿瘤组织中对治疗剂反应的生物学标志物。我们预计这种方法将验证使用低通量异种移植模型来预测对药物的敏感性。如果正确，那么该模型将是无价的，可以发现预测药物反应的生物标志物，并作为选择胰腺癌临床发育的药物的筛查模型。