Oshi Masanori, Okano Maiko, Maiti Aparna, Rashid Omar M, Saito Katsuharu, Kono Koji, Matsuyama Ryusei, Endo Itaru, Takabe Kazuaki
Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
Cancers (Basel). 2020 Feb 14;12(2):444. doi: 10.3390/cancers12020444.
The vast majority of mortality in breast cancer results from distant metastasis. Brain metastases occur in as many as 30% of patients with advanced breast cancer, and the 1-year survival rate of these patients is around 20%. Pre-clinical animal models that reliably reflect the biology of breast cancer brain metastasis are needed to develop and test new treatments for this deadly condition. The patient-derived xenograft (PDX) model maintains many features of a donor tumor, such as intra-tumor heterogeneity, and permits the testing of individualized treatments. However, the establishment of orthotopic PDXs of brain metastasis is procedurally difficult. We have developed a method for generating such PDXs with high tumor engraftment and growth rates. Here, we describe this method and identify variables that affect its outcomes. We also compare the brain-orthotopic PDXs with ectopic PDXs grown in mammary pads of mice, and show that the responsiveness of PDXs to chemotherapeutic reagents can be dramatically affected by the site that they are in.
乳腺癌的绝大多数死亡是由远处转移导致的。多达30%的晚期乳腺癌患者会发生脑转移，这些患者的1年生存率约为20%。需要可靠反映乳腺癌脑转移生物学特性的临床前动物模型来开发和测试针对这种致命疾病的新疗法。患者来源的异种移植（PDX）模型保留了供体肿瘤的许多特征，如肿瘤内异质性，并允许测试个体化治疗。然而，建立脑转移原位PDX在操作上很困难。我们已经开发出一种方法来生成具有高肿瘤植入率和生长率的此类PDX。在此，我们描述这种方法并确定影响其结果的变量。我们还将脑原位PDX与在小鼠乳腺垫中生长的异位PDX进行比较，并表明PDX对化疗试剂的反应性会受到其所在部位的显著影响。
