Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Mol Cancer Ther. 2011 Aug;10(8):1311-6. doi: 10.1158/1535-7163.MCT-11-0233. Epub 2011 Jun 14.
Patients with many advanced solid cancers have very poor prognosis, and improvements in life expectancy are measured only in months. We have recently reported the remarkable clinical outcome of a patient with advanced, gemcitabine-resistant, pancreatic cancer who was later treated with DNA-damaging agents, on the basis of the observation of significant activity of this class of drugs against a personalized tumorgraft generated from the patient's surgically resected tumor. Here, we extend the approach to patients with other advanced cancers. Tumors resected from 14 patients with refractory advanced cancers were propagated in immunodeficient mice and treated with 63 drugs in 232 treatment regimens. An effective treatment regimen in the xenograft model was identified for 12 patients. One patient died before receiving treatment, and the remaining 11 patients received 17 prospectively guided treatments. Fifteen of these treatments resulted in durable partial remissions. In 2 subjects, no effective treatments were found. Overall, there was a remarkable correlation between drug activity in the model and clinical outcome, both in terms of resistance and sensitivity. The data support the use of the personalized tumorgraft model as a powerful investigational platform for therapeutic decision making and to efficiently guide cancer treatment in the clinic.
许多晚期实体瘤患者的预后非常差，预期寿命的延长只能以月来衡量。我们最近报告了一名晚期、吉西他滨耐药性胰腺癌患者的显著临床结果，该患者随后接受了基于对从患者手术切除的肿瘤中生成的个体化肿瘤移植体观察到的此类药物显著活性的 DNA 损伤药物治疗。在这里，我们将这种方法扩展到其他晚期癌症患者。从 14 名难治性晚期癌症患者的肿瘤中切除肿瘤，在免疫缺陷小鼠中传播，并在 232 种治疗方案中用 63 种药物进行治疗。在异种移植模型中确定了 12 名患者的有效治疗方案。一名患者在接受治疗前死亡，其余 11 名患者接受了 17 次前瞻性指导治疗。其中 15 次治疗导致持久的部分缓解。在 2 名患者中，没有发现有效的治疗方法。总的来说，模型中的药物活性与临床结果之间存在显著的相关性，无论是耐药性还是敏感性。这些数据支持将个体化肿瘤移植模型作为治疗决策的强大研究平台，并有效地指导临床癌症治疗。
