Bousquet Guilhem, Janin Anne
UMR-S 1165, Laboratoire de Pathologie, Sorbonne Paris Citx00E9;, Universitx00E9; Paris Diderot, Paris, France.
Pathobiology. 2016;83(4):170-6. doi: 10.1159/000444533. Epub 2016 Mar 25.
The occurrence of metastases severely affects prognosis for patients with cancer, making metastatic disease a daily societal challenge. Because of resistance to drugs, the potential curability with chemotherapy at the metastatic stage remains low. Large genomic analyses to identify new targets have their limitations due to intratumor heterogeneity when they are performed on tumor samples from primary tumors and because the functional value of molecular abnormalities in a cancer is usually not known. Additional tools are thus required for the development of new anticancer agents. The use of preclinical models is a key component of translational research in oncology. For four decades, xenograft models of human cancer cell lines injected subcutaneously in immunocompromised mice have been widely used, with disappointing results for predicting the clinical benefit of a new drug. Patient-derived xenografts are preclinical models rediscovered as innovative pharmacological tools, both for the preclinical development of anticancer drugs and as individual models for personalized treatment of metastatic disease. Here, we review the recent progress reported using patient-derived xenografts for the treatment of metastatic disease, and discuss the feasibility of their implementation in daily oncological care.
转移的发生严重影响癌症患者的预后，使转移性疾病成为日常社会面临的挑战。由于对药物的耐药性，转移性阶段化疗的潜在治愈率仍然很低。在对原发性肿瘤的肿瘤样本进行大基因组分析以识别新靶点时，由于肿瘤内异质性，这些分析存在局限性，而且癌症中分子异常的功能价值通常也不清楚。因此，开发新的抗癌药物需要额外的工具。临床前模型的使用是肿瘤学转化研究的关键组成部分。四十年来，将人类癌细胞系皮下注射到免疫缺陷小鼠体内的异种移植模型被广泛使用，但在预测新药的临床益处方面结果令人失望。患者来源的异种移植是作为创新药理学工具重新发现的临床前模型，既用于抗癌药物的临床前开发，也作为转移性疾病个性化治疗的个体模型。在此，我们综述了使用患者来源的异种移植治疗转移性疾病的最新进展，并讨论了其在日常肿瘤护理中实施的可行性。
