A pilot clinical study of treatment guided by personalized tumorgrafts in patients with advanced cancer.
A pilot clinical study of treatment guided by personalized tumorgrafts in patients with advanced cancer.
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DOI：
10.1158/1535-7163.mct-11-0233
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发表时间：
2011-08
影响因子：
5.7
通讯作者：
Sidransky D
中科院分区：
文献类型：
--
作者：
Hidalgo M;Bruckheimer E;Rajeshkumar NV;Garrido-Laguna I;De Oliveira E;Rubio-Viqueira B;Strawn S;Wick MJ;Martell J;Sidransky D
许多晚期实体癌患者的预后非常差，预期寿命的改善仅以月为单位。我们最近报道了一名晚期吉西他滨耐药胰腺癌患者的显著临床结果，该患者后来接受了DNA损伤剂治疗，这是基于观察到这类药物对患者手术切除肿瘤产生的个性化肿瘤移植物的显著活性。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中切除的肿瘤在免疫缺陷小鼠中繁殖，并在232种治疗方案中用63种药物治疗。在异种移植模型中，确定了12例患者的有效治疗方案。1例患者在接受治疗前死亡，其余11例患者接受了17次前瞻性指导治疗。这些治疗中有15种导致了持久的部分缓解。在2例受试者中，未发现有效的治疗方法。总体而言，模型中的药物活性与临床结果之间存在显著相关性，无论是在耐药性还是敏感性方面。这些数据支持使用个性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。
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.