Tmod-26. developing patient-derived xenograft models of metastatic cancer to the brain

The estimated annual incidence of cancer metastases to the brain is as high as 300,000, about 10 times the incidence of all primary brain cancers combined. At least 20% of all cancers eventually produce metastases to the brain, and approximately 40% of all patients who die of cancer have metastatic brain disease. Once a cancer metastasizes to the brain, median patient survival is 4-8 months. Paradoxically, only about 5% of all cancer research is devoted towards developing better ways of treating metastases. A major limitation in the field has been the relative lack of robust preclinical models. To address this, we have developed a series of patient-derived xenograft (PDX) metastatic brain cancer models, including 3 lung adenocarcinomas, 2 breast carcinomas, 2 melanomas, 2 renal carcinomas, and 1 colorectal adenocarcinoma. This cohort provides representation of the primary cancers that most often metastasize to the brain. Subcutaneous tumors from 3 of these PDX have been used for establishing intracranial tumors in athymic mice, with each producing circumscribed growths whose morphology retains a striking degree of histologic similarity to the patient tumors from which they were derived. FACS analysis of PDX has revealed substantial levels of tumor-initiating cell subpopulations in each. Intracranial tumors from one of these PDX has been tested for radiation response, and 10 Gy (2 Gy x 5) whole brain radiation conferred no significant survival benefit to animal ...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: TUMOR MODELS Source Type: research